Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium Translational Medicine Conference in Israel
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vukovic, V.
Right arrow Articles by Hedley, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vukovic, V.
Right arrow Articles by Hedley, D. W.
[Cancer Research 61, 7394-7398, October 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Hypoxia-inducible Factor-1{alpha} Is an Intrinsic Marker for Hypoxia in Cervical Cancer Xenografts1

Vojislav Vukovic, Hans Kristian Haugland, Trudey Nicklee, Andrew J. Morrison and David W. Hedley2

Departments of Medical Biophysics [V. V., H. K. H., A. J. M., D. W. H.], Medical Oncology and Hematology, [T. N., D. W. H.], and Oncologic Pathology, [D. W. H.], Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada, M5G 2M9

The hypoxia-inducible factor 1 (HIF-1) is known to induce the expression of several proteins linked to the maintenance of oxygen homeostasis, cellular energy metabolism, and tumor progression. Its {alpha} subunit (HIF-1{alpha}) is stabilized under hypoxic conditions and, therefore, might represent an intrinsic marker for tissue hypoxia. Here we report on the spatial relationship between HIF-1{alpha} and the nitroimidazole hypoxia marker EF5 in cervical carcinoma xenografts, and on their spatial relationship to tumor blood vessels. EF5 was administered to mice bearing ME180 and SiHa cervical cancer xenografts. Frozen tumor tissue sections, triple-stained for HIF-1{alpha}, the endothelial cell marker CD31, and EF5, were imaged using wide-field multiparameter immunofluorescence microscopy. Expression levels of EF5 and HIF-1{alpha} were similar in ME180 xenografts, but the percentage of tumor area stained with EF5 was significantly smaller than the percentage of HIF-1{alpha}-positive area in SiHa tumors. In both tumor types the EF5-HIF-1{alpha} overlap was statistically significant, thus confirming their spatial and temporal colocalization. Spatial distribution analysis of EF5 and HIF-1{alpha} is consistent with different pO2 value "thresholds" for EF5 binding and HIF-1{alpha} expression. Summarized, our results indicate that HIF-1{alpha} is a useful intrinsic marker for hypoxia in cervical carcinoma xenografts.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
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]

Home page
 Cancer Res.Home page
D. C. Birle and D. W. Hedley
Suppression of the Hypoxia-Inducible Factor-1 Response in Cervical Carcinoma Xenografts by Proteasome Inhibitors
Cancer Res., February 15, 2007; 67(4): 1735 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 Jpn J Clin OncolHome page
Q.-C. Yang, B.-F. Zeng, Y. Dong, Z.-M. Shi, Z.-M. Jiang, and J. Huang
Overexpression of Hypoxia-Inducible Factor-1{alpha} in Human Osteosarcoma: Correlation with Clinicopathological Parameters and Survival Outcome
Jpn. J. Clin. Oncol., February 1, 2007; 37(2): 127 - 134.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. McMahon, M. Charbonneau, S. Grandmont, D. E. Richard, and C. M. Dubois
Transforming Growth Factor beta1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression
J. Biol. Chem., August 25, 2006; 281(34): 24171 - 24181.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Q. Zhang, S.-Y. Wang, A. C. Nottke, J. V. Rocheleau, D. W. Piston, and R. H. Goodman
Redox sensor CtBP mediates hypoxia-induced tumor cell migration
PNAS, June 13, 2006; 103(24): 9029 - 9033.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. Cristini, H. B. Frieboes, R. Gatenby, S. Caserta, M. Ferrari, and J. Sinek
Morphologic Instability and Cancer Invasion
Clin. Cancer Res., October 1, 2005; 11(19): 6772 - 6779.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Sobhanifar, C. Aquino-Parsons, E. J. Stanbridge, and P. Olive
Reduced Expression of Hypoxia-Inducible Factor-1{alpha} in Perinecrotic Regions of Solid Tumors
Cancer Res., August 15, 2005; 65(16): 7259 - 7266.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Mackay, D. Hedley, P. Major, C. Townsley, M. Mackenzie, M. Vincent, P. Degendorfer, M.-S. Tsao, T. Nicklee, D. Birle, et al.
A Phase II Trial with Pharmacodynamic Endpoints of the Proteasome Inhibitor Bortezomib in Patients with Metastatic Colorectal Cancer
Clin. Cancer Res., August 1, 2005; 11(15): 5526 - 5533.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Y.F. Yau, J. J. Wheeler, K. L. Sutton, and D. W. Hedley
Inhibition of Integrin-Linked Kinase by a Selective Small Molecule Inhibitor, QLT0254, Inhibits the PI3K/PKB/mTOR, Stat3, and FKHR Pathways and Tumor Growth, and Enhances Gemcitabine-Induced Apoptosis in Human Orthotopic Primary Pancreatic Cancer Xenografts
Cancer Res., February 15, 2005; 65(4): 1497 - 1504.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. S. Bindra, P. J. Schaffer, A. Meng, J. Woo, K. Maseide, M. E. Roth, P. Lizardi, D. W. Hedley, R. G. Bristow, and P. M. Glazer
Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells
Mol. Cell. Biol., October 1, 2004; 24(19): 8504 - 8518.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Michiels
Physiological and Pathological Responses to Hypoxia
Am. J. Pathol., June 1, 2004; 164(6): 1875 - 1882.
[Abstract] [Full Text] [PDF]

Home page
 Jpn J Clin OncolHome page
S.-C. Zhang, S.-i. Miyamoto, T. Kamijo, R. Hayashi, T. Hasebe, G. Ishii, M. Fukayama, and A. Ochiai
Intratumor Microvessel Density in Biopsy Specimens Predicts Local Response of Hypopharyngeal Cancer to Radiotherapy
Jpn. J. Clin. Oncol., December 1, 2003; 33(12): 613 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Hedley, M. Pintilie, J. Woo, A. Morrison, D. Birle, A. Fyles, M. Milosevic, and R. Hill
Carbonic Anhydrase IX Expression, Hypoxia, and Prognosis in Patients with Uterine Cervical Carcinomas
Clin. Cancer Res., November 15, 2003; 9(15): 5666 - 5674.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. Imai, A. Horiuchi, C. Wang, K. Oka, S. Ohira, T. Nikaido, and I. Konishi
Hypoxia Attenuates the Expression of E-Cadherin via Up-Regulation of SNAIL in Ovarian Carcinoma Cells
Am. J. Pathol., October 1, 2003; 163(4): 1437 - 1447.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. Bachtiary, M. Schindl, R. Potter, B. Dreier, T. H. Knocke, J. A. Hainfellner, R. Horvat, and P. Birner
Overexpression of Hypoxia-inducible Factor 1{alpha} Indicates Diminished Response to Radiotherapy and Unfavorable Prognosis in Patients Receiving Radical Radiotherapy for Cervical Cancer
Clin. Cancer Res., June 1, 2003; 9(6): 2234 - 2240.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. Acs, P. J. Zhang, C. M. McGrath, P. Acs, J. McBroom, A. Mohyeldin, S. Liu, H. Lu, and A. Verma
Hypoxia-Inducible Erythropoietin Signaling in Squamous Dysplasia and Squamous Cell Carcinoma of the Uterine Cervix and Its Potential Role in Cervical Carcinogenesis and Tumor Progression
Am. J. Pathol., June 1, 2003; 162(6): 1789 - 1806.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. H. A. M. Kaanders, K. I. E. M. Wijffels, H. A. M. Marres, A. S. E. Ljungkvist, L. A. M. Pop, F. J. A. van den Hoogen, P. C. M. de Wilde, J. Bussink, J. A. Raleigh, and A. J. van der Kogel
Pimonidazole Binding and Tumor Vascularity Predict for Treatment Outcome in Head and Neck Cancer
Cancer Res., December 1, 2002; 62(23): 7066 - 7074.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. P. Hui, A. T. C. Chan, F. Pezzella, H. Turley, K.-F. To, T. C. W. Poon, B. Zee, F. Mo, P. M. L. Teo, D. P. Huang, et al.
Coexpression of Hypoxia-inducible Factors 1{alpha} and 2{alpha}, Carbonic Anhydrase IX, and Vascular Endothelial Growth Factor in Nasopharyngeal Carcinoma and Relationship to Survival
Clin. Cancer Res., August 1, 2002; 8(8): 2595 - 2604.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.