| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Early Detection Laboratory and Department of Pathology, Peter MacCallum Cancer Institute, Melbourne 8006, Victoria [T. B., M. C. S., D. J. V.], and Department of Pathology, The University of Melbourne, Parkville 3050, Victoria 3052 [M. C. S., D. J. V.], Australia
 |
ABSTRACT |
|---|
 Top ABSTRACT IntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
|
Introduction |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
The properties of the SRC, AIB1, make it an interesting candidate to help address such issues in breast cancer. AIB1 is located on chromosome 20q12, a common region of amplification in breast cancer. Sequence similarity to SRC-1 and transcription intermediary factor 2, as well as confirmation by functional data, demonstrated AIB1 to belong to the SRC gene family (3) . The presence of AIB1 amplification in some breast tumors suggests that it may act through increased steroid receptor pathway signaling. Alternatively AIB1 overexpression may impact on other nonsteroid receptor pathways relevant to tumor formation in the breast. Indeed, the coactivator function for AIB1 has also been documented for the thyroid and retinoid receptors (6) . Recent biochemical studies with the murine orthologue of AIB1, p/CIP, suggest that the protein exists in a complex with the general transcriptional cointegrator CBP (7) . A functional interaction with other CBP-dependent transcription factors including signal transducers and activators of transcription and activator protein-1 has been demonstrated (7) . Finally, recent findings have also shown that growth factor signaling pathways impinge on SRC binding and coactivator activity through MAPK. Phosphorylation sites have been mapped in both receptors and coactivators (8, 9, 10) . Specifically, MAPK activation of AIB1 stimulates the recruitment of p300 and enhances histone acetyltransferase activity (11) .
Because of its ability to interact with both steroid responsive and nonresponsive nuclear receptors, coupled to the complexity of kinase-mediated growth factor cross-talk, overexpression of AIB1 could potentially perturb signal integration by multiple transduction pathways. To further investigate which one of these functions are important in breast cancer, AIB1 mRNA expression data from 93 unselected primary breast tumors were correlated with protein expression levels, as determined by immunohistochemistry, of steroid receptors (ER and PR), their target genes (PSA and pS2), as well as p53 and the growth factor receptor HER2/neu.
|
Materials and Methods |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
Immunohistochemistry.
Staining was performed on 3-µm sections of formalin-fixed, paraffin
wax-embedded tissue rehydrated through graded alcohols. Antigen
retrieval was used for the ER, PR, AR, HER2/neu, and p53
antibodies, which consists of 2 min of heating under pressure in a
pressure cooker in 10 mM sodium citrate (pH 6.0).
Sections were stained using a DAKO Autostainer (Dako Corp.,
Carpinteria, CA). All of the wash steps used 50
mM Tris-HCl (pH 7.6) and 0.05% Tween 20.
Endogenous peroxidase activity was blocked by incubating sections with
3% hydrogen peroxide for 10 min. A 5-min blocking step (Protein
Blocking Agent; Immonon, Pittsburgh, PA) was used for PSA and pS2. The
primary antibody was applied at the following dilutions for 30 min at
room temperature: ER (1:200; Dako), PR (1:800; Dako), AR (1:50; Dako),
HER2/neu (1:1600; Dako), p53 (DO7) (1:200; Novocastra
Laboratories, Newcastle-Upon-Tyne, United Kingdom), pS2 (1:100;
Novocastra Laboratories), and PSA (1:400; Dako). Biotinylated secondary
antibodies were detected with streptavidin peroxidase by using the LSAB
2 kit (HER2/neu, p53, pS2, and PSA) or the LSAB+ kit (PR,
AR, and ER; Dako). The final color reaction was carried out using
aminoethylcarbazole as a chromogen and counterstained with hematoxylin.
Crystal mount (Biomeda, Foster City, CA) was applied to sections and
dried on a 60°C hotplate. The sections were coverslipped with DPX
mountant.
For all of the antibodies, the intensity of staining and proportion of positive cells were determined for the normal breast epithelium, DCIS, invasive carcinoma, and metastatic components for each case, according to a method described by Armes et al. (12) . Briefly, a semiquantitative estimate of expression levels of the antigen was based on the combined score for the proportion of staining cells and the intensity of staining. The proportion score represented the estimated percentage of positive cells (0, <10%; 1, 11–25%; 2, 26–50%; 3, 51–75%; 4, 76–90%; and 5, >91%.). The intensity score represented the average staining intensity for positive cells (0, none; 1, weak; 2, moderate; and 3, strong). Levels of staining were derived as follows: samples with an intensity score of 0 or having <10% of cells staining were designated negative; and samples with intensity score of 1 in >10% of cells were designated weak. For intensity levels 2 and 3, combined scores of 2–3 were designated as weak, 4–6 as moderate, and 7 or 8 as strong expression. For each antibody, only the cellular compartment described previously as expressing the antigen of interest was scored.
Preparation of Riboprobes.
AIB1 mRNA in situ expression was determined by two
nonoverlapping cDNA fragments used in combination described previously
by Anzick et al. (3)
. cDNA sequences spanning
nucleotides 1733–2579 and 3072–3580 of the AIB1 gene
(GenBank accession number AF012108) were subcloned into the
ClaI and SacI sites of BlueScript vector with T3
and T7 RNA polymerase sites at either end of the insert. A 335-bp
region of ß2-microglobulin was used to assess
RNA integrity (GenBank accession number AB021288) spanning nucleotides
1–335, which was subcloned in the SmaI site of pBluescript
vector. The identity and orientation of the inserts were validated by
sequencing using the Amplicycle sequencing kit (Perkin-Elmer,
Branchenburg, NJ).
Subclones were linearized at one end of the insert with the appropriate restriction enzyme. For each subclone, both sense and antisense probes were synthesized. Approximately 1 µg of linearized template DNA was used for in vitro transcription using 33P-labeled UTP (New England Nuclear, Boston, Massachusetts) according to the manufacturer’s protocol (Stratagene, La Jolla, CA).
Hybridization and Washes.
Sections of formalin-fixed, paraffin-embedded tissue were cut at 5 µm
on aminopropyltriethoxysilane-coated slides and baked at 60°C
for 1 h. Sections were dewaxed in histolene and rehydrated through
graded ethanol. Prior to hybridization, sections were pretreated with
20 µg/ml of proteinase K for 10 min at room temperature in digestion
buffer, 50 mM Tris-HCl (pH 7.5), and 5 mM EDTA
(pH 8.0). The reaction was stopped in 0.2% glycine in PBS buffer for 1
min. Sections were then fixed with 4% paraformaldehyde for 10 min at
room temperature. The sections were dehydrated in increasing
concentrations of ethanol and stored in 100% ethanol at -20°C until
hybridization.
Hybridization was carried out on pretreated tissue sections at 60°C for 48 h in hybridization buffer [0.3 M NaCl, 10 mM Na2HPO4 (pH 6.8), 10 mM Tris-Cl (pH 7.5), 5 mM EDTA (pH 6.8), 50% formamide, 5% dextran sulfate, 100 mg/ml tRNA, and 100 mg/ml single-stranded DNA]. Hybridization buffer (50–100 µl) containing 100–200 ng/ml of each of the two probes was applied to each section. The sections were coverslipped and incubated in a humidified chamber at 60°C for 36–48 h. Posthybridization washes were performed twice at high stringency in hybridization solution [0.3 M NaCl, 10 mM Na2HPO4 (pH 6.8), 10 mM Tris-Cl (pH 7.5), 5 mM EDTA (pH 6.8), and 50% formamide] at 60°C for 20 min each. Nonspecifically bound probe was digested with RNase A. The slides were washed twice in 2x SSC at 65°C, dehydrated in graded ethanols, and air-dried. The slides were then dipped in Kodak NTB-2 emulsion (Eastman Kodak, Rochester, NY), air-dried, and exposed in light proof boxes at 4°C for 4–6 weeks before developing in undiluted Kodak D19 developer according to the manufacturer’s instructions and counterstaining in hematoxylin.
Hybridization Experiments and Analysis.
Each tumor array section was hybridized with the two antisense probes
for AIB1 used in combination. An adjacent section was hybridized with
the sense probes as a negative control. Sections of archival lymph node
were used as positive tissue control to assess reproducibility and
technique performance because AIB1 was found to be highly expressed in
germinal centers. Tumor-infiltrating lymphocytes also served as an
internal positive control. To confirm the presence of intact RNA,
adjacent tissue sections were hybridized with a probe to the
housekeeping gene
ß2-microglobulin. A strong
hybridization signal was present in all sections studied. A 3-point
scoring system was used to assess AIB1 expression levels in each tumor
relative to matched normal breast tissue. Low-level AIB1 mRNA
expression was observed in all histologically normal breast tissues
accompanying the tumors; at high magnification (x400), this consisted
of a few irregularly distributed silver grains over the breast
epithelial cells (averaging 1–4 grains/cell). Accordingly, tumors were
designated to have low AIB1 expression if the same pattern of
irregularly distributed silver grains was present over the tumor cells
and the tumor architecture could not be easily discerned by darkfield
examination at low power. Moderate to high levels were defined as the
distinct clustering of silver grains present over the majority of cells
in the tumor sample, which displayed an easily visible darkfield
pattern consistent with the tumor architecture under low power. At
higher magnification (x400), moderate levels were estimated as a
2–5-fold increase in the number of localized silver grains/cell
relative to matched normal and high estimated to be a >5-fold
increase. For each tumor array, two independent hybridization
experiments were performed. Tumors were only deemed to overexpress AIB1
mRNA if their score in the two independent hybridization experiments
was either moderate or high. AIB1 overexpression was confirmed by
independent hybridization experiments on the original tumor biopsy
blocks used to construct the arrays. Results obtained from whole
biopsies were consistent with those observed on the tissue array. For
analysis purposes, tumors have been subdivided into two groups: those
with low AIB1 expression; and those deemed to overexpress AIB1 as
having high levels.
Statistics.
Statistical comparisons between groups were assessed by two-tailed
Fisher’s exact test or the 
2 test for
independence. Nominal Ps are given without adjustment for
multiple comparisons. Raw data are provided together with the
Ps.
|
Results |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
. Invasive tumors found to have high levels of AIB1 expression also had
high levels of expression present in the corresponding DCIS and
metastatic lesions.
|
. AIB1 overexpression was significantly associated with high tumor
grade, with the majority of tumors expressing high AIB1 mRNA levels
being poorly differentiated grade 3 lesions (P = 0.0006). Tumors with high AIB1 levels tended to occur in
patients with an earlier onset of the disease (
50 years of age at the
time of diagnosis), suggesting a possible link to menopausal status
(P = 0.05). No significant correlation was
observed for the presence or absence of lymph node metastases (Table 1)
.
|
. High levels of AIB1 mRNA expression correlated with the absence of
immunohistochemically detectable ER and PR. AIB1 mRNA was highly
expressed in 15 of 26 (58%) ER-negative tumors compared with only 11
of 55 (20%) ER-positive tumors (P = 0.002).
Similarly for PR, high levels of AIB1 mRNA expression occurred more
frequently in PR-negative tumors 18 of 35 (51%) than in PR-positive
tumors 8 of 48 (17%; P = 0.002). For both
HER2/neu and p53, AIB1 up-regulation was correlated with
moderate to strong staining for these antigens. High levels of AIB1
mRNA were observed in 19 of 38 (50%) tumors with moderate to strong
staining of HER2/neu compared with 7 of 44 (16%) tumors
with weak or negative immunohistochemical expression of the
HER2/neu antigen (P = 0.002). This
difference is further highlighted when the intensity and extent of
staining was considered. For the invasive carcinomas with low levels of
AIB1, only 1 of 56 (2%) expressed HER2/neu strongly,
whereas of the tumors with high AIB1 levels, 10 of 26 (38%) showed
strong HER2/neu staining (P < 0.0001). When this analysis was extended to the DCIS subset, the same
trend was observed (data not shown), with 58% of DCIS (7 of 12)
overexpressing AIB1 also showing strong HER2/neu staining.
In contrast, only 1 of 18 (6%) DCIS cases with low AIB1 had strong
HER2/neu staining (P = 0.003). Of
note, 4 of the 7 DCIS cases with both high HER2/neu and AIB1
were subclassified as high-grade comedo DCIS. This type of DCIS is
characterized histologically by prominent necrosis and by markers of
high-grade malignancy, such as ER/PR negativity and overexpression of
HER2/neu and p53 (13)
. This is consistent with
the features observed in invasive tumors with high AIB1 mRNA; an
example of such an invasive cancer is given in Fig. 2
. For p53, AIB1 was highly expressed in 9 of 15 (60%) tumors with
moderate to strong accumulation of p53 compared with 16 of 66 (24%)
tumors with low p53 staining (P = 0.01). No
significant difference was observed for immunohistochemical staining of
AR, PSA, and pS2 in tumors expressing low levels compared with high
levels of AIB1.
|
|
|
Discussion |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
To first evaluate whether AIB1 overexpression contributes to breast cancer by overstimulating steroid receptor-mediated transactivation, the relationship between AIB1 mRNA expression and immunohistochemical staining for steroid receptors (ER, PR, and AR) and target genes (pS2 and PSA; Ref. 15 and 16 ) was examined. Of particular interest is our significant observation of an inverse relationship between AIB1 mRNA expression and protein staining for ER and PR. The inverse relationship observed in tumors is of interest in the light of immunohistochemical studies showing that the structurally related coactivator SRC-1 in the rat mammary gland is not colocalized with ER but expressed in a subpopulation of epithelial cells distinct from those expressing ER and PR (17) . Taken together, these results suggest that AIB1-mediated pathways not dependent on coexpression of ER and PR protein (at the levels usually detected by immunohistochemistry) may be predominately active in the mammary gland and in a significant subset of breast cancers.
To further examine the relationship between AIB1 mRNA up-regulation and other factors that may influence the efficacy of antiestrogen therapy or potentially offer a point for signaling cross-talk, we investigated the same tumor cases for coexpression of HER2/neu, a receptor tyrosine kinase that is overexpressed in 20–30% of breast cancers (18) . Overexpression of HER2/neu in breast cancer is inversely correlated with ER levels and predicts clinical resistance to the antiestrogen tamoxifen (19) . We detected a strong correlation between AIB1 mRNA and HER2/neu protein overexpression, which is consistent with the inverse correlation observed for ER and PR. This relationship may simply reflect an association with high tumor grade or, alternatively, may be an indicator of some form of cooperative cross-talk between AIB1 and HER2/neu. The latter possibility offers interesting insight. Newman et al. (20) , using the ER-positive breast cancer cell line ZR75-1, demonstrated that in antiestrogenic media the structurally related coactivator SRC-1 activates the HER2/neu enhancer. This coactivator competition study suggests that AIB1 may contribute to the transcriptional up-regulation of HER2/neu. Alternatively, cross-talk may occur at the protein level. The precise molecular mechanisms are still not clear; however, evidence supports the notion that steroid receptor phosphorylation (through MAPK), a downstream target of HER2/neu, promotes coactivator recruitment (8) . Tremblay et al. (9) demonstrated that MAPK induced phosphorylation of specific serine residues within the NH2-terminal AF1 transactivation domain of ERß enhances coactivator recruitment and estrogen-independent transactivation. Other studies have extended these findings to demonstrate in prostate cancer models the enhancement of AR-mediated transactivation in the presence of increased HER2/neu/MAPK activity, again possibly because of enhanced AR-coactivator interaction (21 , 22) . In addition to nuclear receptors, MAPK phosphorylation sites have also been mapped in coactivators, specifically SRC-1 and AIB1 (10 , 11) . MAPK phosphorylation of AIB1 has been shown to stimulate its intrinsic histone acetyl transferase activity and the recruitment of the transcriptional cointegrator p300 (11) . These experiments, taken together with our findings of a strong correlation between AIB1 and HER2/neu in breast cancer, suggest that HER2/neu is acting upstream of MAPK phosphorylation of AIB1 and may promote its coactivator activity and interaction with specific steroid receptors or other yet to be defined transcription factors. This may potentially lead to autonomous (ligand independent) and/or growth factor-modulated transactivation of target genes, accounting for estrogen-independent tumor growth. Genes involved in these processes could be developed as markers to assess disease progression.
The view that AIB1 dysregulation cooperates with other oncogenic events during breast cancer progression has also been put forward by Bautista et al. (14) . Unlike our study, which focuses on AIB1 mRNA expression, these workers concentrated on AIB1 gene amplification (which occurs in only 5% of breast tumors) and found a strong correlation between amplification of AIB1 and MDM2. The MDM2 gene negatively regulates p53, and its amplification in tumors is thought to be equivalent to p53 inactivation (23) . This is consistent with our findings of a correlation between high AIB1 and strong protein staining for the tumor suppressor gene p53 (which is thought to accompany p53 inactivation and protein stabilization). The transcriptional cointegrators p300/CBP, with which AIB1 forms a complex, regulate the transactivation function and protein abundance of p53 (24 , 25) , further emphasizing the potential interaction between the AIB1 and p53/MDM2 pathways. Whether AIB1 in complex with CBP/p300 contributes to these functions remains to be elucidated but may have important implications for more precisely understanding AIB1 action in breast cancer.
In conclusion, our study reports up-regulation of AIB1 gene transcripts in 30% of nonselected human breast carcinomas. The new findings outlined here indicate that AIB1 overexpression occurs in a minority of steroid receptor-expressing tumors and suggest a possible convergence of AIB1 with other pathways involving HER2/neu overexpression and p53 inactivation, which may be involved in estrogen-independent growth. Further studies to examine the role of AIB1 overexpression in patients with known response to endocrine therapy and the identification of transcription factors specifically affected by AIB1 dysregulation are now necessary to further define how this gene impacts on the clinical phenotype and biology of breast cancer.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 This work was supported by the University of
Melbourne and the Peter MacCallum Cancer Institute. 
2 To whom requests for reprints should be
addressed, at The Murdoch Children’s Research Institute, Royal
Children’s Hospital, 10th Floor, Flemington Road, Parkville, Victoria
3052, Australia. Phone: 61-3-8341-6231; Fax: 61-3-9348-1391; E-mail: venterd{at}murdoch.unimelb.edu
3 The abbreviations used are: SRC, steroid
receptor coactivator; AIB1, amplified in breast cancer 1; ER, estrogen
receptor-
; PR, progesterone receptor; AR, androgen receptor; CBP,
cAMP-response element binding protein; MAPK, mitogen-activated protein
kinase; MDM2, murine double minute; DCIS, ductal carcinoma in
situ; PSA, prostate-specific antigen.
Received 8/21/00. Accepted 12/21/00.
|
REFERENCES |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. Yang and M. J Young The mineralocorticoid receptor and its coregulators J. Mol. Endocrinol., August 1, 2009; 43(2): 53 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Alkner, P.-O. Bendahl, D. Grabau, K. Lovgren, O. Stal, L. Ryden, M. Ferno, and on behalf of the South Swedish and South-East Swed AIB1 is a predictive factor for tamoxifen response in premenopausal women Ann. Onc., July 23, 2009; (2009) mdp293v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Heck, J. Rom, V. Thewes, N. Becker, B. Blume, H. P. Sinn, U. Deuschle, C. Sohn, A. Schneeweiss, and P. Lichter Estrogen-Related Receptor {alpha} Expression and Function Is Associated with the Transcriptional Coregulator AIB1 in Breast Carcinoma Cancer Res., June 15, 2009; 69(12): 5186 - 5193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A Boorjian, H. V Heemers, I. Frank, S. A Farmer, L. J Schmidt, T. J Sebo, and D. J Tindall Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder Endocr. Relat. Cancer, March 1, 2009; 16(1): 123 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Oh, J. T. Lahusen, C. D. Chien, M. P. Fereshteh, X. Zhang, S. Dakshanamurthy, J. Xu, B. L. Kagan, A. Wellstein, and A. T. Riegel Tyrosine Phosphorylation of the Nuclear Receptor Coactivator AIB1/SRC-3 Is Enhanced by Abl Kinase and Is Required for Its Activity in Cancer Cells Mol. Cell. Biol., November 1, 2008; 28(21): 6580 - 6593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Fereshteh, M. T. Tilli, S. E. Kim, J. Xu, B. W. O'Malley, A. Wellstein, P. A. Furth, and A. T. Riegel The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for Neu (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice Cancer Res., May 15, 2008; 68(10): 3697 - 3706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Song, I.-m. Shih, R. Salani, D. W. Chan, and Z. Zhang Annexin XI Is Associated with Cisplatin Resistance and Related to Tumor Recurrence in Ovarian Cancer Patients Clin. Cancer Res., November 15, 2007; 13(22): 6842 - 6849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lahusen, M. Fereshteh, A. Oh, A. Wellstein, and A. T. Riegel Epidermal Growth Factor Receptor Tyrosine Phosphorylation and Signaling Controlled by a Nuclear Receptor Coactivator, Amplified in Breast Cancer 1 Cancer Res., August 1, 2007; 67(15): 7256 - 7265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mussi, C. Yu, B. W. O'Malley, and J. Xu Stimulation of Steroid Receptor Coactivator-3 (SRC-3) Gene Overexpression by a Positive Regulatory Loop of E2F1 and SRC-3 Mol. Endocrinol., December 1, 2006; 20(12): 3105 - 3119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan, C.-T. Yu, M. Ozen, M. Ittmann, S. Y. Tsai, and M.-J. Tsai Steroid Receptor Coactivator-3 and Activator Protein-1 Coordinately Regulate the Transcription of Components of the Insulin-Like Growth Factor/AKT Signaling Pathway. Cancer Res., November 15, 2006; 66(22): 11039 - 11046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. El Messaoudi, E. Fabbrizio, C. Rodriguez, P. Chuchana, L. Fauquier, D. Cheng, C. Theillet, L. Vandel, M. T. Bedford, and C. Sardet Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene PNAS, September 5, 2006; 103(36): 13351 - 13356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mani, A. S. Oh, E. T. Bowden, T. Lahusen, K. L. Lorick, A. M. Weissman, R. Schlegel, A. Wellstein, and A. T. Riegel E6AP Mediates Regulated Proteasomal Degradation of the Nuclear Receptor Coactivator Amplified in Breast Cancer 1 in Immortalized Cells. Cancer Res., September 1, 2006; 66(17): 8680 - 8686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Horiguchi, S. Arai, T. Nishihara, and J.-i. Nishikawa AIB1 Promotes DNA Replication by JNK Repression and AKT Activation during Cellular Stress J. Biochem., September 1, 2006; 140(3): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Louie, A. S. Revenko, J. X. Zou, J. Yao, and H.-W. Chen Direct Control of Cell Cycle Gene Expression by Proto-Oncogene Product ACTR, and Its Autoregulation Underlies Its Transforming Activity Mol. Cell. Biol., May 15, 2006; 26(10): 3810 - 3823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Spurdle, A. C. Antoniou, L. Kelemen, H. Holland, S. Peock, M. R. Cook, P. L. Smith, M. H. Greene, J. Simard, M. Plourde, et al. The AIB1 Polyglutamine Repeat Does Not Modify Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers Cancer Epidemiol. Biomarkers Prev., January 1, 2006; 15(1): 76 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Zheng, R.-C. Wu, C. L. Smith, and B. W. O'Malley Rapid Estrogen-Induced Phosphorylation of the SRC-3 Coactivator Occurs in an Extranuclear Complex Containing Estrogen Receptor Mol. Cell. Biol., September 15, 2005; 25(18): 8273 - 8284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Zhou, J. Yan, W. Luo, G. Ayala, S.-H. Lin, H. Erdem, M. Ittmann, S. Y. Tsai, and M.-J. Tsai SRC-3 Is Required for Prostate Cancer Cell Proliferation and Survival Cancer Res., September 1, 2005; 65(17): 7976 - 7983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, S. Wang, D. Medina, B. W. O'Malley, and J. Xu Mice Lacking the Amplified in Breast Cancer 1/Steroid Receptor Coactivator-3 Are Resistant to Chemical Carcinogen-Induced Mammary Tumorigenesis Cancer Res., September 1, 2005; 65(17): 7993 - 8002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Burwinkel, M. Wirtenberger, R. Klaes, R. K. Schmutzler, E. Grzybowska, A. Forsti, B. Frank, J. L. Bermejo, P. Bugert, B. Wappenschmidt, et al. Association of NCOA3 Polymorphisms with Breast Cancer Risk Clin. Cancer Res., March 15, 2005; 11(6): 2169 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Osborne and R. Schiff Estrogen-Receptor Biology: Continuing Progress and Therapeutic Implications J. Clin. Oncol., March 10, 2005; 23(8): 1616 - 1622. [Full Text] [PDF]
|
|
|
|
|
|
M. T. Tilli, R. Reiter, A. S. Oh, R. T. Henke, K. McDonnell, G. I. Gallicano, P. A. Furth, and A. T. Riegel Overexpression of an N-Terminally Truncated Isoform of the Nuclear Receptor Coactivator Amplified in Breast Cancer 1 Leads to Altered Proliferation of Mammary Epithelial Cells in Transgenic Mice Mol. Endocrinol., March 1, 2005; 19(3): 644 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Oh, H.-J. List, R. Reiter, A. Mani, Y. Zhang, E. Gehan, A. Wellstein, and A. T. Riegel The Nuclear Receptor Coactivator AIB1 Mediates Insulin-like Growth Factor I-induced Phenotypic Changes in Human Breast Cancer Cells Cancer Res., November 15, 2004; 64(22): 8299 - 8308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F J Fleming, E Myers, G Kelly, T B Crotty, E W McDermott, N J O'Higgins, A D K Hill, and L S Young Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1 J. Clin. Pathol., October 1, 2004; 57(10): 1069 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Henke, B. R. Haddad, S. E. Kim, J. D. Rone, A. Mani, J. M. Jessup, A. Wellstein, A. Maitra, and A. T. Riegel Overexpression of the Nuclear Receptor Coactivator AIB1 (SRC-3) during Progression of Pancreatic Adenocarcinoma Clin. Cancer Res., September 15, 2004; 10(18): 6134 - 6142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Louie, J. X. Zou, A. Rabinovich, and H.-W. Chen ACTR/AIB1 Functions as an E2F1 Coactivator To Promote Breast Cancer Cell Proliferation and Antiestrogen Resistance Mol. Cell. Biol., June 15, 2004; 24(12): 5157 - 5171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goel and R. Janknecht Concerted Activation of ETS Protein ER81 by p160 Coactivators, the Acetyltransferase p300 and the Receptor Tyrosine Kinase HER2/Neu J. Biol. Chem., April 9, 2004; 279(15): 14909 - 14916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, H. Zhang, A. V. Lee, B. W. O'Malley, and J. Xu AIB1/SRC-3 Deficiency Affects Insulin-Like Growth Factor I Signaling Pathway and Suppresses v-Ha-ras-induced Breast Cancer Initiation and Progression in Mice Cancer Res., March 1, 2004; 64(5): 1875 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Smith and B. W. O'Malley Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators Endocr. Rev., February 1, 2004; 25(1): 45 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou, Y. Hashimoto, I. Kwak, S. Y. Tsai, and M.-J. Tsai Role of the Steroid Receptor Coactivator SRC-3 in Cell Growth Mol. Cell. Biol., November 1, 2003; 23(21): 7742 - 7755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu and Q. Li Review of the in Vivo Functions of the p160 Steroid Receptor Coactivator Family Mol. Endocrinol., September 1, 2003; 17(9): 1681 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, A. Hoque, R. Z. Luo, J. Yuan, Z. Lu, A. Nishimoto, J. Liu, A. A. Sahin, S. M. Lippman, R. C. Bast Jr., et al. Loss of the Expression of the Tumor Suppressor Gene ARHI Is Associated with Progression of Breast Cancer Clin. Cancer Res., September 1, 2003; 9(10): 3660 - 3666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Girault, F. Lerebours, S. Amarir, S. Tozlu, M. Tubiana-Hulin, R. Lidereau, and I. Bieche Expression Analysis of Estrogen Receptor {alpha} Coregulators in Breast Carcinoma: Evidence That NCOR1 Expression Is Predictive of the Response to Tamoxifen Clin. Cancer Res., April 1, 2003; 9(4): 1259 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Osborne, V. Bardou, T. A. Hopp, G. C. Chamness, S. G. Hilsenbeck, S. A. W. Fuqua, J. Wong, D. C. Allred, G. M. Clark, and R. Schiff Role of the Estrogen Receptor Coactivator AIB1 (SRC-3) and HER-2/neu in Tamoxifen Resistance in Breast Cancer J Natl Cancer Inst, March 5, 2003; 95(5): 353 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Konecny, G. Pauletti, M. Pegram, M. Untch, S. Dandekar, Z. Aguilar, C. Wilson, H.-M. Rong, I. Bauerfeind, M. Felber, et al. Quantitative Association Between HER-2/neu and Steroid Hormone Receptors in Hormone Receptor-Positive Primary Breast Cancer J Natl Cancer Inst, January 15, 2003; 95(2): 142 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Belbin, B. Singh, I. Barber, N. Socci, B. Wenig, R. Smith, M. B. Prystowsky, and G. Childs Molecular Classification of Head and Neck Squamous Cell Carcinoma Using cDNA Microarrays Cancer Res., February 1, 2002; 62(4): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Reiter, A. Wellstein, and A. T. Riegel An Isoform of the Coactivator AIB1 That Increases Hormone and Growth Factor Sensitivity Is Overexpressed in Breast Cancer J. Biol. Chem., October 19, 2001; 276(43): 39736 - 39741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. List, K. J. Lauritsen, R. Reiter, C. Powers, A. Wellstein, and A. T. Riegel Ribozyme Targeting Demonstrates That the Nuclear Receptor Coactivator AIB1 Is a Rate-limiting Factor for Estrogen-dependent Growth of Human MCF-7 Breast Cancer Cells J. Biol. Chem., June 22, 2001; 276(26): 23763 - 23768. [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 |
