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Expression by the Epidermal Growth Factor/Phosphatidylinositol 3-Kinase/PTEN/AKT/FRAP Pathway in Human Prostate Cancer Cells: Implications for Tumor Angiogenesis and Therapeutics1
The Johns Hopkins Oncology Center, Brady Urological Institute [H. Z., C. H., J. W. S.] and Departments of Pediatrics and Medicine and Institute of Genetic Medicine [K. C., D. F., E. L., G. L. S.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, and Laboratory of Molecular Oncology, The Rockefeller University, New York, New York 10021 [M-M. G.]
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ABSTRACT |
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 Top ABSTRACT IntroductionMaterials and MethodsResultsDiscussionREFERENCES |
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, the regulated subunit of the
transcription factor HIF-1, is blocked by LY294002 and rapamycin,
inhibitors of PI3K and FRAP, respectively. HIF-1-dependent gene
transcription is blocked by dominant-negative AKT or PI3K and by
wild-type PTEN, whereas transcription is stimulated by constitutively
active AKT or dominant-negative PTEN. LY294002 and rapamycin also
inhibit growth factor- and mitogen-induced secretion of vascular
endothelial growth factor, the product of a known HIF-1 target gene,
thus linking the PI3K/PTEN/AKT/FRAP pathway, HIF-1, and tumor
angiogenesis. These data indicate that pharmacological agents that
target PI3K, AKT, or FRAP in tumor cells inhibit HIF-1 expression
and that such inhibition may contribute to therapeutic efficacy. |
Introduction |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
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protein, HIF-1-dependent
transcriptional activity, and VEGF protein in human PCA cells. These
results provide a mechanism contributing to the overexpression of
HIF-1 in PCA and other solid cancers (8)
and have
important implications regarding cancer progression and therapy. |
Materials and Methods |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
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Immunoblot Assays.
Cells (0.5–1.0 x 106) were seeded onto
150-mm tissue culture dishes (Falcon) and incubated for 36–48 h in
complete media (except for AKT assays, in which cells were plated
directly in media with 0.1% FBS). The cells were incubated in media
with 0–0.1% FBS for 24 h and then given fresh media with
0–0.1% FBS alone or with 10% FBS, EGF (Life Technologies, Inc.),
PMA, or 4-PMA, either alone or with LY294002, PD098059, rapamycin,
or wortmannin (Alexis Corp.), for 6–8 h. For analysis of HIF-1
expression, nuclear extracts were prepared, and aliquots were analyzed
using monoclonal antibody H167 (Novus Biologicals, Inc.) as
described previously (8)
. Blots were stripped and
incubated with anti-topoisomerase I antibodies (TopoGEN). Aliquots of
whole cell lysates were subjected to immunoblot assay using anti-AKT
and phospho-AKT antibodies (New England Biolabs). All immunoblots were
developed using enhanced chemiluminescence reagents (Amersham).
Transient Transfection Assays.
DU145 cells were seeded onto 24-well culture plates at a density of
4 x 104 cells/well and incubated for
24 h in complete media. The cells were transfected with 12.5 ng of
control plasmid pTK-RL (Promega) containing the herpes simplex virus
thymidine kinase promoter and Renilla reniformis (sea pansy)
luciferase coding sequences; 100 ng of reporter plasmid p2.1 containing
a 68-bp hypoxia response element from the ENO1 gene, an SV40
promoter, and Photinus pyralis (firefly) luciferase coding
sequences (12)
; and 500 ng of pCEP4 (Invitrogen) or
expression vector encoding AKT-MYR, AKT (K179M), wild-type PTEN, PTEN
(C124S), or p85
(13, 14, 15, 16)
. KD-AKT, C124S PTEN, and
p85 have each been shown to have dominant negative effects in cells
expressing the respective wild-type protein. Cells were exposed to
plasmid DNA for 8 h in 1 µl of Fugene-6 (Boehringer Mannheim).
Cells were then incubated in DMEM with 0.1% FBS for 16 h,
followed by exposure to 10% FBS, 100 nM PMA, and 1%
O2 or no treatment for 24 h. Cells were lysed in 100
µl of buffer, and Dual-Luciferase (Promega) reporter assays were
performed on 20-µl aliquots.
VEGF ELISA Assays.
TSU cells were seeded onto 6-well culture plates at a density of
4 x 104 cells per well, incubated for
24 h in complete media, and then given serum-free media for
16 h, followed by fresh serum-free media, either alone or with
10% FBS, EGF, or PMA alone or with LY294002 or rapamycin, for 24 h. Conditioned media were removed for storage at -80°C, and cells
were counted. VEGF protein concentration in the media was determined by
ELISA using a commercial kit (R&D Systems).
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Results |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
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protein and HIF-1 DNA-binding activity under
nonhypoxic conditions, and expression is further increased in response
to hypoxia (11)
. Potential clinical implications of these
findings were underscored by the immunohistochemical demonstration that
HIF-1 is overexpressed (relative to adjacent normal tissue) in
common human solid tumors, including PCA (8)
. HIF-1
expression was also induced in transformed cells exposed to EGF,
fibroblast growth factor 2, IGF-1, or IGF-2 (10)
. Because
of the known role of EGF signaling via the PI3K pathway (reviewed in
Ref. 2
), we investigated whether up-regulation of this pathway
contributed to increased HIF-1 expression in PCA cells. As an
initial means of modulating the activity of this pathway, we examined
the effect of serum starvation and stimulation. TSU, PC-3, DU145, and
PPC-1 cells were cultured at low density in serum-free medium for
24 h and then exposed to 0% or 10% FBS for 6 h. All four
cell lines demonstrated some degree of HIF-1 expression under
serum-free conditions that increased in response to serum stimulation
(Fig. 1A)
. To examine responses to specific mitogens, cells were exposed to 100
nM PMA or 20 ng/ml EGF. PMA strongly induced HIF-1
expression in DU145, TSU, and PPC-1 cells (Fig. 1B)
.
Exposure of TSU cells to 20 ng/ml EGF also markedly induced HIF-1
expression, whereas the effect of EGF on DU145 and PPC-1 cells was more
modest. In DU145 and TSU cells, similar levels of HIF-1 expression
were induced by exposure to PMA or hypoxia, whereas the biologically
inactive 4-PMA had no effect (Fig. 1C)
.
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expression, PCA cells were exposed to LY294002 or wortmannin,
inhibitors of PI3K, or to rapamycin, an inhibitor of FRAP
(17)
, a signaling molecule downstream of PI3K (Fig. 2A)
. PC-3 cells were cultured in 0.1% FBS in the presence of varying
concentrations of LY294002 under hypoxic (1% O2) or
nonhypoxic (20% O2) conditions. HIF-1 expression under
nonhypoxic conditions was partially inhibited by 1 µM
LY294002 and completed inhibited by 10 µM LY294002 (Fig. 2B
,
top panel). In contrast, hypoxia-induced HIF-1
expression was only partially inhibited by 10 µM LY294002
and was more completely inhibited by 50 µM LY294002.
Wortmannin was a more potent inhibitor in nonhypoxic cells because
partial inhibition and complete inhibition of HIF-1 expression were
observed in the presence of 10 and 100 nM wortmannin,
respectively, in nonhypoxic cells, whereas only modest inhibition was
observed with 200 nM wortmannin in hypoxic cells (Fig. 2B
,
middle panel). Rapamycin was the most potent drug
tested; it inhibited HIF-1 expression at concentrations of 10 and 50
nM in nonhypoxic and hypoxic cells, respectively (Fig. 2B
,
bottom panel). Induction of HIF-1 expression in PC-3
or TSU cells exposed to either 10% FBS, 100 nM PMA, or 20
ng/ml EGF was completely inhibited by 50 µM LY294002
(Fig. 2C)
. PMA-induced HIF-1 expression was completely
inhibited in the presence of 10 µM LY294002 or 10
nM rapamycin (data not shown). Under the experimental
conditions used, none of the inhibitors caused cell death during the
study period as determined by analysis of cellular ATP concentration,
morphology, or trypan blue exclusion (data not shown). Taken together,
these results suggest that basal and mitogen-induced HIF-1
expression in PCA cells is highly dependent on PI3K activity, whereas
other signaling pathways stimulate hypoxia-induced expression.
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. In TSU cells cultured in serum-free media, a modest
degree of AKT phosphorylation was detected, which increased in response
to EGF stimulation (Fig. 3
,top panel, Lanes 1 and 2). These data are
consistent with previous reports of EGF-stimulated AKT activity in PCA
cells (18
, 19)
. Both basal and EGF-induced AKT
phosphorylation were blocked by LY294002 (Lane 3). In
contrast, the mitogen-activated protein kinase/extracellular
signal-regulated kinase (MEK) inhibitor PD098059 (Fig. 2A)
had no inhibitory effect (Fig. 3
, top panel, Lane 4),
suggesting that mitogen-activated protein kinase activity is not
required in these cells. In PC-3 cells, which show the highest level of
HIF-1 expression under nonhypoxic conditions (Fig. 1A
;
Ref. 11
), the extent of AKT phosphorylation was even greater than that
in TSU cells but was nevertheless completely blocked by treatment with
LY294002 (Fig. 3
, top panel, Lanes 5 and 6),
whereas treatment with rapamycin (which inhibits the pathway downstream
of AKT) or PD098059 had no inhibitory effect (Lanes 7 and
8). Hypoxia had no effect on AKT phosphorylation in PC-3
cells (Lanes 9–12). Total AKT protein levels were not
affected by EGF, LY294002, PD098059, or hypoxia (Fig. 3
, bottom
panel).
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in the presence of empty expression vector. In contrast, reporter gene
activity was below basal levels in PMA-stimulated cells transfected
with vector encoding KD-AKT, a catalytically-inactive (kinase-dead)
form of AKT containing a K179M missense mutation (14)
;
wild-type PTEN; or p85, a dominant-negative form of the PI3K p85
regulatory subunit (16)
. Reporter activity was induced
17-fold by hypoxia, and this response was partially inhibited by
KD-AKT, wild-type PTEN, or PI3K-p85 (Fig. 4B)
. These
results, which are consistent with the effects of the PI3K inhibitor
LY294002 on HIF-1 expression reported above (Fig. 2)
, demonstrate
that PI3K and PTEN-regulated AKT activity are required for
HIF-1-mediated transcription in response to PMA.
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,
0.1% FBS (Fig. 4D)
, or 0.1% FBS with 100 nM
PMA (Fig. 4E)
. Under all three conditions, both
constitutively active AKT and dominant-negative PTEN induced reporter
gene expression, with the greatest response observed in PMA-stimulated
cells.
To demonstrate that the PI3K-mediated induction of HIF-1
transcriptional activity results in biological activity, the secretion
of VEGF protein by TSU cells was analyzed by ELISA. Cells were
serum-starved for 6 h and then exposed to no treatment, 10% FBS,
50 nM PMA, or 20 ng/ml EGF for 24 h. Despite the short
incubation time, FBS, PMA, and EGF each increased VEGF protein levels
in the tissue culture supernatant, and PMA resulted in the greatest
induction (Fig. 4F)
, as was also observed with respect to
HIF-1 expression (Fig. 1)
. Treatment with low concentrations of
either LY294002 (10 µM) or rapamycin (10 nM)
markedly inhibited the induction of VEGF expression by FBS, PMA, or EGF
(Fig. 4F)
, similar to the effect of these inhibitors on
mitogen-induced HIF-1 expression (Fig. 2)
. Thus, both
HIF-1-dependent gene transcription (Fig. 4A–E)
and the
expression of a HIF-1-regulated gene product (Fig. 4F)
are
modulated by the activity of the PI3K/AKT/FRAP pathway in PCA cells.
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Discussion |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
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protein, HIF-1
transcriptional activity, and VEGF protein expression in PCA cells.
HIF-1 protein expression is regulated by ubiquitination and
proteasomal degradation (reviewed in Ref. 7
). Additional studies are
required to determine whether this process is modulated by
PI3K/AKT/FRAP activity and, if so, whether such modulation involves
direct phosphorylation of HIF-1.
These results provide a molecular basis for the previously
reported expression of HIF-1 under nonhypoxic conditions in PCA
cells (11)
. It is likely that, in vivo,
increased activity of the PI3K pathway contributes to the dramatic
overexpression of HIF-1 in PCA and other human cancers
(8)
. The tumor suppressor PTEN, which negatively regulates
the PI3K pathway, is a target for mutation in PCA, breast cancer,
gliomas, and other tumor types (3, 4, 5, 6
, 19, 20, 21)
. In PCA,
inactivation of PTEN expression is associated with disease progression
and angiogenesis (3
, 4) . It is well established that HIF-1
activates genes encoding glucose transporters, glycolytic enzymes, heme
oxygenase-1, IGF-2, IGF-binding proteins, inducible nitric oxide
synthase, transferrin, and VEGF, all of which have been implicated in
tumor progression (reviewed in Ref. 7
). In particular, the association
between PTEN loss of function and angiogenesis may be explained by the
induction of HIF-1, leading to increased VEGF expression. Colon
cancer cells transfected with a HIF-1 expression vector demonstrated
increased VEGF mRNA expression as well as increased growth and
angiogenesis of tumor xenografts (22)
.
In addition to PTEN, loss of function mutations in tumor suppressor
genes encoding VHL (23)
and p53 (8
, 22)
result in increased expression of HIF-l and VEGF. Gain of
function mutations in oncogenes also induce HIF-1 expression, as
demonstrated for v-src (24)
and inferred for
autocrine activation of EGF and IGF-I receptors, based on the results
presented above and in previous studies (9
, 10)
. Induction
of transcription via the VEGF gene promoter by activated
H-RAS also requires PI3K/AKT activity and an intact HIF-1 binding site
(16)
. Thus, V-SRC, H-RAS, and receptor tyrosine kinases
all lead to increased activity of both the PI3K/AKT pathway (2
, 18
, 19
, 25)
and HIF-1.
Several conclusions can be drawn from the available data. First, in
human tumors, increased expression of HIF-1 is induced by genetic
alterations as well as by physiological stimulation. Second, expression
of HIF-1 may play a major role in promoting angiogenesis and metabolic
adaptation in PCA and other common solid tumors. In addition to the
data regarding the effects of increased HIF-1 expression cited
above, loss of HIF-1 expression in tumor cells is associated with
decreased xenograft growth and angiogenesis (24
, 26)
.
Third, whereas genetic alterations affecting signal transduction
pathways are highly variable among human tumors, increased expression
of HIF-1 may represent a common final pathway. Fourth, if HIF-1
mediated angiogenesis and metabolic adaptation play important roles in
tumor progression, as suggested by previous studies (7
, 8
, 22, 23, 24
, 26)
, then pharmacological inhibition of HIF-1 activity
may represent a useful treatment strategy. Furthermore, the effect of
PI3K/AKT/FRAP pathway inhibitors on HIF-1 expression may provide a
basis for therapeutic efficacy.
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ACKNOWLEDGMENTS |
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expression vector. We thank Kimberly Heaney for technical assistance. |
FOOTNOTES |
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1 Supported by NIH Prostate Cancer SPORE Grant
CA-58236; NIH Grant RO1-HL55338 and Children’s Brain Tumor Foundation
(to G. L. S.); AEGON Gift for Accelerated Breast and Prostate
Cancer Research, CaP CURE Foundation, and Department of Defense Grant
DAMD 17-98-1-8475 (to J. W. S.). 
2 To whom requests for reprints should be
addressed, at Brady Urological Institute, Marburg 409, Johns Hopkins
Hospital, 600 North Wolfe Street, Baltimore, MD 21287-2411.
3 The abbreviations used are: EGF, epidermal
growth factor; PI3K, phosphatidylinositol 3-kinase; FRAP,
FKBP-rapamycin-associated protein; PCA, prostate cancer; HIF-1,
hypoxia-inducible factor 1; VEGF, vascular endothelial growth factor;
FBS, fetal bovine serum; IGF, insulin-like growth factor; PMA, phorbol
12-myristate 13-acetate.
Received 12/ 2/99. Accepted 2/ 3/00.
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REFERENCES |
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in common human cancers and their metastases. Cancer Res., 59: 5830-5835, 1999. and insulin-like growth factor 2. Cancer Res., 59: 3915-3918, 1999. in rat and human prostate cancer. Cancer Res., 58: 5280-5284, 1998.. Genes Dev., 14: 34-44, 2000.This article has been cited by other articles:
|
|
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|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
K.-Y. Chang, M.-R. Shen, M.-Y. Lee, W.-L. Wang, W.-C. Su, W.-C. Chang, and B.-K. Chen Epidermal Growth Factor-activated Aryl Hydrocarbon Receptor Nuclear Translocator/HIF-1{beta} Signal Pathway Up-regulates Cyclooxygenase-2 Gene Expression Associated with Squamous Cell Carcinoma J. Biol. Chem., April 10, 2009; 284(15): 9908 - 9916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Semenza Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1 Physiology, April 1, 2009; 24(2): 97 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lu, K. Zhang, S. Chen, and W. Wen Grape seed extract inhibits VEGF expression via reducing HIF-1{alpha} protein expression Carcinogenesis, April 1, 2009; 30(4): 636 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 K. X. Knaup, K. Jozefowski, R. Schmidt, W. M. Bernhardt, A. Weidemann, J. S. Juergensen, C. Warnecke, K.-U. Eckardt, and M. S. Wiesener Mutual Regulation of Hypoxia-Inducible Factor and Mammalian Target of Rapamycin as a Function of Oxygen Availability Mol. Cancer Res., January 1, 2009; 7(1): 88 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Greenberger, I. D. Horak, D. Filpula, P. Sapra, M. Westergaard, H. F. Frydenlund, C. Albaek, H. Schroder, and H. Orum A RNA antagonist of hypoxia-inducible factor-1{alpha}, EZN-2968, inhibits tumor cell growth Mol. Cancer Ther., November 1, 2008; 7(11): 3598 - 3608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ader, L. Brizuela, P. Bouquerel, B. Malavaud, and O. Cuvillier Sphingosine Kinase 1: A New Modulator of Hypoxia Inducible Factor 1{alpha} during Hypoxia in Human Cancer Cells Cancer Res., October 15, 2008; 68(20): 8635 - 8642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-B. Han, H. Ren, H. Zhao, Y. Chi, K. Chen, B. Zhou, Y.-j. Liu, L. Zhang, B. Xu, B. Liu, et al. Hypoxia-inducible factor (HIF)-1{alpha} directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF) Carcinogenesis, October 1, 2008; 29(10): 1853 - 1861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mahadevan, G. Powis, E. A. Mash, B. George, V. M. Gokhale, S. Zhang, K. Shakalya, L. Du-Cuny, M. Berggren, M. A. Ali, et al. Discovery of a novel class of AKT pleckstrin homology domain inhibitors Mol. Cancer Ther., September 1, 2008; 7(9): 2621 - 2632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gallo, G. F. Zannoni, I. De Stefano, M. Mosca, C. Ferlini, E. Mantuano, and G. Scambia Soy Phytochemicals Decrease Nonsmall Cell Lung Cancer Growth In Female Athymic Mice J. Nutr., July 1, 2008; 138(7): 1360 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Plathow and W. A. Weber Tumor Cell Metabolism Imaging J. Nucl. Med., June 1, 2008; 49(Suppl_2): 43S - 63S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, Y. Lu, K. Liang, T. Pan, J. Mendelsohn, and Z. Fan Requirement of hypoxia-inducible factor-1{alpha} down-regulation in mediating the antitumor activity of the anti-epidermal growth factor receptor monoclonal antibody cetuximab Mol. Cancer Ther., May 1, 2008; 7(5): 1207 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Fritz, T.-M. Lin, and R. E. Peterson The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates Carcinogenesis, May 1, 2008; 29(5): 1077 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. P. Deudero, C. Caramelo, M. C. Castellanos, F. Neria, R. Fernandez-Sanchez, O. Calabia, S. Penate, and F. R. Gonzalez-Pacheco Induction of Hypoxia-inducible Factor 1{alpha} Gene Expression by Vascular Endothelial Growth Factor J. Biol. Chem., April 25, 2008; 283(17): 11435 - 11444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scortegagna, C. Cataisson, R. J. Martin, D. J. Hicklin, R. D. Schreiber, S. H. Yuspa, and J. M. Arbeit HIF-1{alpha} regulates epithelial inflammation by cell autonomous NF{kappa}B activation and paracrine stromal remodeling Blood, April 1, 2008; 111(7): 3343 - 3354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Emerling, F. Weinberg, J.-L. Liu, T. W. Mak, and N. S. Chandel PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a) PNAS, February 19, 2008; 105(7): 2622 - 2627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Furuta, S. K. Pai, R. Zhan, S. Bandyopadhyay, M. Watabe, Y.-Y. Mo, S. Hirota, S. Hosobe, T. Tsukada, K. Miura, et al. Fatty Acid Synthase Gene Is Up-regulated by Hypoxia via Activation of Akt and Sterol Regulatory Element Binding Protein-1 Cancer Res., February 15, 2008; 68(4): 1003 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Carroll and M. Ashcroft Regulation of Angiogenic Factors by HDM2 in Renal Cell Carcinoma Cancer Res., January 15, 2008; 68(2): 545 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Garlich, P. De, N. Dey, J. D. Su, X. Peng, A. Miller, R. Murali, Y. Lu, G. B. Mills, V. Kundra, et al. A Vascular Targeted Pan Phosphoinositide 3-Kinase Inhibitor Prodrug, SF1126, with Antitumor and Antiangiogenic Activity Cancer Res., January 1, 2008; 68(1): 206 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Koh, T. Spivak-Kroizman, S. Venturini, S. Welsh, R. R. Williams, D. L. Kirkpatrick, and G. Powis Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1{alpha} Mol. Cancer Ther., January 1, 2008; 7(1): 90 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Lee, W. H. Kim, J. Jung, S. J. Cho, J.-W. Park, J. Kim, H.-Y. Chung, M. S. Chang, and S. Y. Nam A hypoxia-independent up-regulation of hypoxia-inducible factor-1 by AKT contributes to angiogenesis in human gastric cancer Carcinogenesis, January 1, 2008; 29(1): 44 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rapisarda and G. Melillo HIF-1 Inhibitors: Novel Opportunities for Cancer Therapy ASCO Educational Book, January 1, 2008; 2008(1): 543 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
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T. Klatte, D. B. Seligson, S. B. Riggs, J. T. Leppert, M. K. Berkman, M. D. Kleid, H. Yu, F. F. Kabbinavar, A. J. Pantuck, and A. S. Belldegrun Hypoxia-Inducible Factor 1{alpha} in Clear Cell Renal Cell Carcinoma Clin. Cancer Res., December 15, 2007; 13(24): 7388 - 7393. [Abstract] [Full Text] [PDF]
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 R. J. Anand, S. C. Gribar, J. Li, J. W. Kohler, M. F. Branca, T. Dubowski, C. P. Sodhi, and D. J. Hackam Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1{alpha}-dependent manner J. Leukoc. Biol., November 1, 2007; 82(5): 1257 - 1265. [Abstract] [Full Text] [PDF]
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 M. Nasimuzzaman, G. Waris, D. Mikolon, D. G. Stupack, and A. Siddiqui Hepatitis C Virus Stabilizes Hypoxia-Inducible Factor 1{alpha} and Stimulates the Synthesis of Vascular Endothelial Growth Factor J. Virol., October 1, 2007; 81(19): 10249 - 10257. [Abstract] [Full Text] [PDF]
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 H. W. J. Young, O. W. Williams, D. Chandra, L. K. Bellinghausen, G. Perez, A. Suarez, M. J. Tuvim, M. G. Roy, S. N. Alexander, S. J. Moghaddam, et al. Central Role of Muc5ac Expression in Mucous Metaplasia and Its Regulation by Conserved 5' Elements Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 273 - 290. [Abstract] [Full Text] [PDF]
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 M. Milkiewicz, J. L. Doyle, T. Fudalewski, E. Ispanovic, M. Aghasi, and T. L. Haas HIF-1{alpha} and HIF-2{alpha} play a central role in stretch-induced but not shear-stress-induced angiogenesis in rat skeletal muscle J. Physiol., September 1, 2007; 583(2): 753 - 766. [Abstract] [Full Text] [PDF]
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Q. Zhang, X. Tang, Z.-F. Zhang, R. Velikina, S. Shi, and A. D. Le Nicotine Induces Hypoxia-Inducible Factor-1{alpha} Expression in Human Lung Cancer Cells via Nicotinic Acetylcholine Receptor Mediated Signaling Pathways Clin. Cancer Res., August 15, 2007; 13(16): 4686 - 4694. [Abstract] [Full Text] [PDF]
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 Y. Ma, C. Hu, A. T. Riegel, S. Fan, and E. M. Rosen Growth Factor Signaling Pathways Modulate BRCA1 Repression of Estrogen Receptor-{alpha} Activity Mol. Endocrinol., August 1, 2007; 21(8): 1905 - 1923. [Abstract] [Full Text] [PDF]
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 M.-C. Lauzier, E. L. Page, M. D. Michaud, and D. E. Richard Differential Regulation of Hypoxia-Inducible Factor-1 through Receptor Tyrosine Kinase Transactivation in Vascular Smooth Muscle Cells Endocrinology, August 1, 2007; 148(8): 4023 - 4031. [Abstract] [Full Text] [PDF]
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 D. Flugel, A. Gorlach, C. Michiels, and T. Kietzmann Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1{alpha} and Mediates Its Destabilization in a VHL-Independent Manner Mol. Cell. Biol., May 1, 2007; 27(9): 3253 - 3265. [Abstract] [Full Text] [PDF]
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A. A. Kazi and R. D. Koos Estrogen-Induced Activation of Hypoxia-Inducible Factor-1{alpha}, Vascular Endothelial Growth Factor Expression, and Edema in the Uterus Are Mediated by the Phosphatidylinositol 3-Kinase/Akt Pathway Endocrinology, May 1, 2007; 148(5): 2363 - 2374. [Abstract] [Full Text] [PDF]
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X. Tang, Q. Zhang, J. Nishitani, J. Brown, S. Shi, and A. D. Le Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Hypoxia-Inducible Factor 1{alpha} Protein Accumulation and Vascular Endothelial Growth Factor Expression in Human Cervical Carcinoma Cells Clin. Cancer Res., May 1, 2007; 13(9): 2568 - 2576. [Abstract] [Full Text] [PDF]
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 J. J. Lum, T. Bui, M. Gruber, J. D. Gordan, R. J. DeBerardinis, K. L. Covello, M. C. Simon, and C. B. Thompson The transcription factor HIF-1{alpha} plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis Genes & Dev., May 1, 2007; 21(9): 1037 - 1049. [Abstract] [Full Text] [PDF]
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R. T. Kurmasheva, F. C. Harwood, and P. J. Houghton Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors Mol. Cancer Ther., May 1, 2007; 6(5): 1620 - 1628. [Abstract] [Full Text] [PDF]
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K. Murata and M. Moriyama Isoleucine, an Essential Amino Acid, Prevents Liver Metastases of Colon Cancer by Antiangiogenesis Cancer Res., April 1, 2007; 67(7): 3263 - 3268. [Abstract] [Full Text] [PDF]
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J. Fang, Q. Zhou, L.-Z. Liu, C. Xia, X. Hu, X. Shi, and B.-H. Jiang Apigenin inhibits tumor angiogenesis through decreasing HIF-1{alpha} and VEGF expression Carcinogenesis, April 1, 2007; 28(4): 858 - 864. [Abstract] [Full Text] [PDF]
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 F. Wang, S. S. Li, R. Segersvard, L. Strommer, K.-G. Sundqvist, J. Holgersson, and J. Permert Hypoxia Inducible Factor-1 Mediates Effects of Insulin on Pancreatic Cancer Cells and Disturbs Host Energy Homeostasis Am. J. Pathol., February 1, 2007; 170(2): 469 - 477. [Abstract] [Full Text] [PDF]
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W. G. Kaelin Jr. The von Hippel-Lindau Tumor Suppressor Protein and Clear Cell Renal Carcinoma Clin. Cancer Res., January 15, 2007; 13(2): 680s - 684s. [Abstract] [Full Text] [PDF]
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Q. Zhou, L.-Z. Liu, B. Fu, X. Hu, X. Shi, J. Fang, and B.-H. Jiang Reactive oxygen species regulate insulin-induced VEGF and HIF-1{alpha} expression through the activation of p70S6K1 in human prostate cancer cells Carcinogenesis, January 1, 2007; 28(1): 28 - 37. [Abstract] [Full Text] [PDF]
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 M. Ramanathan, G. Pinhal-Enfield, I. Hao, and S. J. Leibovich Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2A Receptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF Promoter Mol. Biol. Cell, January 1, 2007; 18(1): 14 - 23. [Abstract] [Full Text] [PDF]
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H. Tanaka, M. Yamamoto, N. Hashimoto, M. Miyakoshi, S. Tamakawa, M. Yoshie, Y. Tokusashi, K. Yokoyama, Y. Yaginuma, and K. Ogawa Hypoxia-Independent Overexpression of Hypoxia-Inducible Factor 1{alpha} as an Early Change in Mouse Hepatocarcinogenesis Cancer Res., December 1, 2006; 66(23): 11263 - 11270. [Abstract] [Full Text] [PDF]
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D. C. Birle and D. W. Hedley Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts. Mol. Cancer Ther., October 1, 2006; 5(10): 2494 - 2502. [Abstract] [Full Text] [PDF]
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N. Pore, A. K. Gupta, G. J. Cerniglia, Z. Jiang, E. J. Bernhard, S. M. Evans, C. J. Koch, S. M. Hahn, and A. Maity Nelfinavir Down-regulates Hypoxia-Inducible Factor 1{alpha} and VEGF Expression and Increases Tumor Oxygenation: Implications for Radiotherapy. Cancer Res., September 15, 2006; 66(18): 9252 - 9259. [Abstract] [Full Text] [PDF]
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I. Serganova, J. Humm, C. Ling, and R. Blasberg Tumor hypoxia imaging. Clin. Cancer Res., September 15, 2006; 12(18): 5260 - 5264. [Full Text] [PDF]
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D. T. Jones, C. W. Pugh, S. Wigfield, M. F.G. Stevens, and A. L. Harris Novel Thioredoxin Inhibitors Paradoxically Increase Hypoxia-Inducible Factor-{alpha} Expression but Decrease Functional Transcriptional Activity, DNA Binding, and Degradation. Clin. Cancer Res., September 15, 2006; 12(18): 5384 - 5394. [Abstract] [Full Text] [PDF]
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X.-H. Peng, P. Karna, Z. Cao, B.-H. Jiang, M. Zhou, and L. Yang Cross-talk between Epidermal Growth Factor Receptor and Hypoxia-inducible Factor-1{alpha} Signal Pathways Increases Resistance to Apoptosis by Up-regulating Survivin Gene Expression J. Biol. Chem., September 8, 2006; 281(36): 25903 - 25914. [Abstract] [Full Text] [PDF]
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 K S Kimbro and J W Simons Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 739 - 749. [Abstract] [Full Text] [PDF]
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R. P Singh and R. Agarwal Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr. Relat. Cancer, September 1, 2006; 13(3): 751 - 778. [Abstract] [Full Text] [PDF]
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D. T. Jones and A. L. Harris Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol. Cancer Ther., September 1, 2006; 5(9): 2193 - 2202. [Abstract] [Full Text] [PDF]
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G. Melillo Inhibiting Hypoxia-Inducible Factor 1 for Cancer Therapy Mol. Cancer Res., September 1, 2006; 4(9): 601 - 605. [Abstract] [Full Text] [PDF]
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 V. H. Haase Hypoxia-inducible factors in the kidney Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281. [Abstract] [Full Text] [PDF]
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 C.-C. Chang, M.-T. Lin, B.-R. Lin, Y.-M. Jeng, S.-T. Chen, C.-Y. Chu, R. J. Chen, K.-J. Chang, P.-C. Yang, and M.-L. Kuo Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis. J Natl Cancer Inst, July 19, 2006; 98(14): 984 - 995. [Abstract] [Full Text] [PDF]
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J. Riss, C. Khanna, S. Koo, G. V.R. Chandramouli, H. H. Yang, Y. Hu, D. E. Kleiner, A. Rosenwald, C. F. Schaefer, S. A. Ben-Sasson, et al. Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma. Cancer Res., July 15, 2006; 66(14): 7216 - 7224. [Abstract] [Full Text] [PDF]
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D. Freeman, R. Lesche, N. Kertesz, S. Wang, G. Li, J. Gao, M. Groszer, H. Martinez-Diaz, N. Rozengurt, G. Thomas, et al. Genetic Background Controls Tumor Development in Pten-Deficient Mice. Cancer Res., July 1, 2006; 66(13): 6492 - 6496. [Abstract] [Full Text] [PDF]
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N. Pore, Z. Jiang, H.-K. Shu, E. Bernhard, G. D. Kao, and A. Maity Akt1 Activation Can Augment Hypoxia-Inducible Factor-1{alpha} Expression by Increasing Protein Translation through a Mammalian Target of Rapamycin-Independent Pathway Mol. Cancer Res., July 1, 2006; 4(7): 471 - 479. [Abstract] [Full Text] [PDF]
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N. Solban, S. K. Pal, S. K. Alok, C. K. Sung, and T. Hasan Mechanistic Investigation and Implications of Photodynamic Therapy Induction of Vascular Endothelial Growth Factor in Prostate Cancer Cancer Res., June 1, 2006; 66(11): 5633 - 5640. [Abstract] [Full Text] [PDF]
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J. Litz and G. W. Krystal Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1{alpha} activity and vascular endothelial growth factor expression in small cell lung cancer cells. Mol. Cancer Ther., June 1, 2006; 5(6): 1415 - 1422. [Abstract] [Full Text] [PDF]
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 J. A. Garcia HIFing the Brakes: Therapeutic Opportunities for Treatment of Human Malignancies Sci. Signal., May 30, 2006; 2006(337): pe25 - pe25. [Abstract] [Full Text] [PDF]
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 Q. Zhang, O. W. Moe, J. A. Garcia, and C. C. W. Hsia Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L880 - L889. [Abstract] [Full Text] [PDF]
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G. Li, Y. Hu, Y. Huo, M. Liu, D. Freeman, J. Gao, X. Liu, D.-C. Wu, and H. Wu PTEN Deletion Leads to Up-regulation of a Secreted Growth Factor Pleiotrophin J. Biol. Chem., April 21, 2006; 281(16): 10663 - 10668. [Abstract] [Full Text] [PDF]
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 B. N. Gomperts and R. M. Strieter CXC Chemokines in Angiogenesis and Metastases Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 11 - 18. [Full Text] [PDF]
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M. Calvani, A. Rapisarda, B. Uranchimeg, R. H. Shoemaker, and G. Melillo Hypoxic induction of an HIF-1{alpha}-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells Blood, April 1, 2006; 107(7): 2705 - 2712. [Abstract] [Full Text] [PDF]
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N. Pore, Z. Jiang, A. Gupta, G. Cerniglia, G. D. Kao, and A. Maity EGFR Tyrosine Kinase Inhibitors Decrease VEGF Expression by Both Hypoxia-Inducible Factor (HIF)-1-Independent and HIF-1-Dependent Mechanisms. Cancer Res., March 15, 2006; 66(6): 3197 - 3204. [Abstract] [Full Text] [PDF]
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F. Kaper, N. Dornhoefer, and A. J. Giaccia Mutations in the PI3K/PTEN/TSC2 Pathway Contribute to Mammalian Target of Rapamycin Activity and Increased Translation under Hypoxic Conditions Cancer Res., February 1, 2006; 66(3): 1561 - 1569. [Abstract] [Full Text] [PDF]
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D. T. Dang, F. Chen, L. B. Gardner, J. M. Cummins, C. Rago, F. Bunz, S. V. Kantsevoy, and L. H. Dang Hypoxia-Inducible Factor-1{alpha} Promotes Nonhypoxia-Mediated Proliferation in Colon Cancer Cells and Xenografts Cancer Res., February 1, 2006; 66(3): 1684 - 1693. [Abstract] [Full Text] [PDF]
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N. Skuli, S. Monferran, C. Delmas, I. Lajoie-Mazenc, G. Favre, C. Toulas, and E. Cohen-Jonathan-Moyal Activation of RhoB by Hypoxia Controls Hypoxia-Inducible Factor-1{alpha} Stabilization through Glycogen Synthase Kinase-3 in U87 Glioblastoma Cells Cancer Res., January 1, 2006; 66(1): 482 - 489. [Abstract] [Full Text] [PDF]
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 H. Acker The oxygen sensing signal cascade under the influence of reactive oxygen species Phil Trans R Soc B, December 29, 2005; 360(1464): 2201 - 2210. [Abstract] [Full Text] [PDF]
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 A. Dekanty, S. Lavista-Llanos, M. Irisarri, S. Oldham, and P. Wappner The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-{alpha}/Sima J. Cell Sci., December 1, 2005; 118(23): 5431 - 5441. [Abstract] [Full Text] [PDF]
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 K. S. Lee, H. S. Park, S. J. Park, S. R. Kim, K. H. Min, S. M. Jin, K.-H. Park, U.-H. Kim, C. Y. Kim, and Y. C. Lee A Prodrug of Cysteine, L-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma Mol. Pharmacol., November 1, 2005; 68(5): 1281 - 1290. [Abstract] [Full Text] [PDF]
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R. H. Wenger, D. P. Stiehl, and G. Camenisch Integration of Oxygen Signaling at the Consensus HRE Sci. Signal., October 18, 2005; 2005(306): re12 - re12. [Abstract] [Full Text] [PDF]
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D. Kong, E. J. Park, A. G. Stephen, M. Calvani, J. H. Cardellina, A. Monks, R. J. Fisher, R. H. Shoemaker, and G. Melillo Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity Cancer Res., October 1, 2005; 65(19): 9047 - 9055. [Abstract] [Full Text] [PDF]
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Q. Zhang, X. Tang, Q. Y. Lu, Z. F. Zhang, J. Brown, and A. D. Le Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1{alpha} and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells Mol. Cancer Ther., October 1, 2005; 4(10): 1465 - 1474. [Abstract] [Full Text] [PDF]
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Y.-T. Huang, S.-L. Pan, J.-H. Guh, Y.-L. Chang, F.-Y. Lee, S.-C. Kuo, and C.-M. Teng YC-1 suppresses constitutive nuclear factor-{kappa}B activation and induces apoptosis in human prostate cancer cells Mol. Cancer Ther., October 1, 2005; 4(10): 1628 - 1635. [Abstract] [Full Text] [PDF]
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 A. Maloyan, L. Eli-Berchoer, G. L. Semenza, G. Gerstenblith, M. D. Stern, and M. Horowitz HIF-1{alpha}-targeted pathways are activated by heat acclimation and contribute to acclimation-ischemic cross-tolerance in the heart Physiol Genomics, September 21, 2005; 23(1): 79 - 88. [Abstract] [Full Text] [PDF]
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J.-Y. Han, S. H. Oh, F. Morgillo, J. N. Myers, E. Kim, W. K. Hong, and H.-Y. Lee Hypoxia-inducible Factor 1{alpha} and Antiangiogenic Activity of Farnesyltransferase Inhibitor SCH66336 in Human Aerodigestive Tract Cancer J Natl Cancer Inst, September 7, 2005; 97(17): 1272 - 1286. [Abstract] [Full Text] [PDF]
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D. Trisciuoglio, A. Iervolino, G. Zupi, and D. Del Bufalo Involvement of PI3K and MAPK Signaling in bcl-2-induced Vascular Endothelial Growth Factor Expression in Melanoma Cells Mol. Biol. Cell, September 1, 2005; 16(9): 4153 - 4162. [Abstract] [Full Text] [PDF]
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 A. A. Adjei and M. Hidalgo Intracellular Signal Transduction Pathway Proteins As Targets for Cancer Therapy J. Clin. Oncol., August 10, 2005; 23(23): 5386 - 5403. [Abstract] [Full Text] [PDF]
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D. W. Nelson, H. Cao, Y. Zhu, B. Sunar-Reeder, C. Y.H. Choi, J. D. Faix, J. M. Brown, A. C. Koong, A. J. Giaccia, and Q.-T. Le A Noninvasive Approach for Assessing Tumor Hypoxia in Xenografts: Developing a Urinary Marker for Hypoxia Cancer Res., July 15, 2005; 65(14): 6151 - 6158. [Abstract] [Full Text] [PDF]
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 R. Busca, E. Berra, C. Gaggioli, M. Khaled, K. Bille, B. Marchetti, R. Thyss, G. Fitsialos, L. Larribere, C. Bertolotto, et al. Hypoxia-inducible factor 1{alpha} is a new target of microphthalmia-associated transcription factor (MITF) in melanoma cells J. Cell Biol., July 4, 2005; 170(1): 49 - 59. [Abstract] [Full Text] [PDF]
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 T Gaber, R Dziurla, R Tripmacher, G R Burmester, and F Buttgereit Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! Ann Rheum Dis, July 1, 2005; 64(7): 971 - 980. [Abstract] [Full Text] [PDF]
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B. M. Emerling, L. C. Platanias, E. Black, A. R. Nebreda, R. J. Davis, and N. S. Chandel Mitochondrial Reactive Oxygen Species Activation of p38 Mitogen-Activated Protein Kinase Is Required for Hypoxia Signaling Mol. Cell. Biol., June 15, 2005; 25(12): 4853 - 4862. [Abstract] [Full Text] [PDF]
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A. Xiao, C. Yin, C. Yang, A. Di Cristofano, P. P. Pandolfi, and T. Van Dyke Somatic Induction of Pten Loss in a Preclinical Astrocytoma Model Reveals Major Roles in Disease Progression and Avenues for Target Discovery and Validation Cancer Res., June 15, 2005; 65(12): 5172 - 5180. [Abstract] [Full Text] [PDF]
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 H. Nakamura, Y. Makino, K. Okamoto, L. Poellinger, K. Ohnuma, C. Morimoto, and H. Tanaka TCR Engagement Increases Hypoxia-Inducible Factor-1{alpha} Protein Synthesis via Rapamycin-Sensitive Pathway under Hypoxic Conditions in Human Peripheral T Cells J. Immunol., June 15, 2005; 174(12): 7592 - 7599. [Abstract] [Full Text] [PDF]
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R. J. Phillips, J. Mestas, M. Gharaee-Kermani, M. D. Burdick, A. Sica, J. A. Belperio, M. P. Keane, and R. M. Strieter Epidermal Growth Factor and Hypoxia-induced Expression of CXC Chemokine Receptor 4 on Non-small Cell Lung Cancer Cells Is Regulated by the Phosphatidylinositol 3-Kinase/PTEN/AKT/Mammalian Target of Rapamycin Signaling Pathway and Activation of Hypoxia Inducible Factor-1{alpha} J. Biol. Chem., June 10, 2005; 280(23): 22473 - 22481. [Abstract] [Full Text] [PDF]
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 G. W. Cole Jr, A. M. Alleva, R. M. Reddy, J. B. Maxhimer, J. Zuo, D. S. Schrump, and D. M. Nguyen The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1010 - 1017. [Abstract] [Full Text] [PDF]
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C. Treins, S. Giorgetti-Peraldi, J. Murdaca, M.-N. Monthouel-Kartmann, and E. Van Obberghen Regulation of Hypoxia-Inducible Factor (HIF)-1 Activity and Expression of HIF Hydroxylases in Response to Insulin-Like Growth Factor I Mol. Endocrinol., May 1, 2005; 19(5): 1304 - 1317. [Abstract] [Full Text] [PDF]
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K. M. Connor, S. Subbaram, K. J. Regan, K. K. Nelson, J. E. Mazurkiewicz, P. J. Bartholomew, A. E. Aplin, Y.-T. Tai, J. Aguirre-Ghiso, S. C. Flores, et al. Mitochondrial H2O2 Regulates the Angiogenic Phenotype via PTEN Oxidation J. Biol. Chem., April 29, 2005; 280(17): 16916 - 16924. [Abstract] [Full Text] [PDF]
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Y. M. Li, B. P. Zhou, J. Deng, Y. Pan, N. Hay, and M.-C. Hung A Hypoxia-Independent Hypoxia-Inducible Factor-1 Activation Pathway Induced by Phosphatidylinositol-3 Kinase/Akt in HER2 Overexpressing Cells Cancer Res., April 15, 2005; 65(8): 3257 - 3263. [Abstract] [Full Text] [PDF]
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G. J. Kelloff, J. M. Hoffman, B. Johnson, H. I. Scher, B. A. Siegel, E. Y. Cheng, B. D. Cheson, J. O'Shaughnessy, K. Z. Guyton, D. A. Mankoff, et al. Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development Clin. Cancer Res., April 15, 2005; 11(8): 2785 - 2808. [Abstract] [Full Text] [PDF]
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) or
exposed to 10% FBS (
), 20 ng/ml EGF (
), or
50 nM PMA (
) for 24 h, either alone (O)
or in the presence of 10 µM LY294002 (L) or 10
nM rapamycin (R). VEGF protein concentrations in
conditioned media were determined by ELISA and corrected for cell
number. Each bar represents the mean of VEGF concentrations
from duplicate plates of cells, which differed by 
20% in all
cases.