© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 5, 353-361,
March 5, 2003
© 2003 Oxford University Press
ARTICLE |
Role of the Estrogen Receptor Coactivator AIB1 (SRC-3) and HER-2/neu in Tamoxifen Resistance in Breast Cancer
Affiliation of authors: C. K. Osborne, S. A. W. Fuqua (Departments of Medicine and Molecular and Cellular Biology and the Breast Center), V. Bardou, T. A. Hopp, G. C. Chamness, S. G. Hilsenbeck, R. Schiff, G. M. Clark (Department of Medicine and the Breast Center), J. Wong (Department of Molecular and Cellular Biology), D. C. Allred (Department of Pathology and the Breast Center), Baylor College of Medicine, Houston, TX.
Correspondence to: C. Kent Osborne, M.D., Baylor College of Medicine, One Baylor Plaza, BCM 600, Houston, TX 77030 (e-mail: kosborne{at}breastcenter.tmc.edu).
Background: AIB1 (SRC-3) is an estrogen receptor (ER) coactivator that, when overexpressed in cultured cells, can reduce the antagonist activity of tamoxifen-bound ERs. Signaling through the HER-2 receptor pathway activates AIB1 by phosphorylation. To determine whether high AIB1 expression alone or together with HER-2 reduces the effectiveness of tamoxifen in breast cancer patients, we quantified expression of AIB1 and HER-2 in tumors from breast cancer patients with long-term clinical follow-up who received either no adjuvant therapy or adjuvant tamoxifen therapy after breast cancer surgery. Methods: AIB1 and HER-2 protein levels in tumors from 316 breast cancer patients were determined using western blot analysis. Molecular variables (e.g., expression of AIB1, ER, progesterone receptor, p53, Bcl-2), tumor characteristics, and patient outcome were assessed using Spearman rank correlation. Disease-free survival (DFS) curves were derived from Kaplan–Meier estimates, and the curves were compared by log-rank tests. The effect of AIB1 on DFS adjusted for other prognostic factors was assessed by multivariable analysis using the Cox proportional hazards model. All statistical tests were two-sided. Results: High AIB1 expression in patients not receiving adjuvant tamoxifen therapy was associated with better prognosis and longer DFS (P = .018, log-rank test). In contrast, for patients who did receive tamoxifen therapy, high AIB1 expression was associated with worse DFS (P = .049, log-rank test), which is indicative of tamoxifen resistance. The test for interaction between AIB1 expression and tamoxifen therapy was statistically significant (P = .004). When expression of AIB1 and HER-2 were considered together, patients whose tumors expressed high levels of both AIB1 and HER-2 had worse outcomes with tamoxifen therapy than all other patients combined (P = .002, log-rank test). Conclusions: The antitumor activity of tamoxifen in patients with breast cancer may be determined, in part, by tumor levels of AIB1 and HER-2. Thus, AIB1 may be an important diagnostic and therapeutic target.
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R. M. O'Regan, C. Osipo, E. Ariazi, E. S. Lee, K. Meeke, C. Morris, A. Bertucci, M. A.B. Sarker, R. Grigg, and V. C. Jordan Development and therapeutic options for the treatment of raloxifene-stimulated breast cancer in athymic mice. Clin. Cancer Res., April 1, 2006; 12(7): 2255 - 2263. [Abstract] [Full Text] [PDF]
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S. P. Linke, T. M. Bremer, C. D. Herold, G. Sauter, and C. Diamond A Multimarker Model to Predict Outcome in Tamoxifen-Treated Breast Cancer Patients Clin. Cancer Res., February 15, 2006; 12(4): 1175 - 1183. [Abstract] [Full Text] [PDF]
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S. Jiang, R. Meyer, K. Kang, C. K. Osborne, J. Wong, and S. Oesterreich Scaffold Attachment Factor SAFB1 Suppresses Estrogen Receptor {alpha}-Mediated Transcription in Part via Interaction with Nuclear Receptor Corepressor Mol. Endocrinol., February 1, 2006; 20(2): 311 - 320. [Abstract] [Full Text] [PDF]
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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]
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C.-C. Lin, Y.-L. Tsai, M.-T. Huang, Y.-P. Lu, C.-T. Ho, S.-F. Tseng, and S.-C. Teng Inhibition of estradiol-induced mammary proliferation by dibenzoylmethane through the E2-ER-ERE-dependent pathway Carcinogenesis, January 1, 2006; 27(1): 131 - 136. [Abstract] [Full Text] [PDF]
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T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]
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N. Normanno, M. Di Maio, E. De Maio, A. De Luca, A. de Matteis, A. Giordano, F. Perrone, and on behalf of the NCI-Naples Breast Cancer Group Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 721 - 747. [Abstract] [Full Text] [PDF]
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M. Dowsett, J. Cuzick, C. Wale, T. Howell, J. Houghton, and M. Baum Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study J. Clin. Oncol., October 20, 2005; 23(30): 7512 - 7517. [Abstract] [Full Text] [PDF]
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X. Cui, R. Schiff, G. Arpino, C. K. Osborne, and A. V. Lee Biology of Progesterone Receptor Loss in Breast Cancer and Its Implications for Endocrine Therapy J. Clin. Oncol., October 20, 2005; 23(30): 7721 - 7735. [Abstract] [Full Text] [PDF]
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H. Kishimoto, Z. Wang, P. Bhat-Nakshatri, D. Chang, R. Clarke, and H. Nakshatri The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1{alpha}/CXCL12 Carcinogenesis, October 1, 2005; 26(10): 1706 - 1715. [Abstract] [Full Text] [PDF]
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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]
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C. Osipo, K. Meeke, H. Liu, D. Cheng, S. Lim, A. Weichel, and V. C. Jordan Trastuzumab Therapy for Tamoxifen-Stimulated Endometrial Cancer Cancer Res., September 15, 2005; 65(18): 8504 - 8513. [Abstract] [Full Text] [PDF]
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G. Arpino, H. Weiss, A. V. Lee, R. Schiff, S. De Placido, C. K. Osborne, and R. M. Elledge Estrogen Receptor-Positive, Progesterone Receptor-Negative Breast Cancer: Association With Growth Factor Receptor Expression and Tamoxifen Resistance J Natl Cancer Inst, September 7, 2005; 97(17): 1254 - 1261. [Abstract] [Full Text] [PDF]
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K-M Rau, H-Y Kang, T-L Cha, S A Miller, and M-C Hung The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers Endocr. Relat. Cancer, September 1, 2005; 12(3): 511 - 532. [Abstract] [Full Text] [PDF]
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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]
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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]
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N. C. Peterson, M. D. Servinsky, A. Christian, Z. Peng, W. Qiu, J. Mann, J. Dicello, and D. L. Huso Tamoxifen resistance and Her2/neu expression in an aged, irradiated rat breast carcinoma model Carcinogenesis, September 1, 2005; 26(9): 1542 - 1552. [Abstract] [Full Text] [PDF]
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J. Baselga, J. Albanell, A. Ruiz, A. Lluch, P. Gascon, V. Guillem, S. Gonzalez, S. Sauleda, I. Marimon, J. M. Tabernero, et al. Phase II and Tumor Pharmacodynamic Study of Gefitinib in Patients with Advanced Breast Cancer J. Clin. Oncol., August 10, 2005; 23(23): 5323 - 5333. [Abstract] [Full Text] [PDF]
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Y. M. Shah, M. Al-Dhaheri, Y. Dong, C. Ip, F. E. Jones, and B. G. Rowan Selenium disrupts estrogen receptor {alpha} signaling and potentiates tamoxifen antagonism in endometrial cancer cells and tamoxifen-resistant breast cancer cells Mol. Cancer Ther., August 1, 2005; 4(8): 1239 - 1249. [Abstract] [Full Text] [PDF]
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L. Ryden, K. Jirstrom, P.-O. Bendahl, M. Ferno, B. Nordenskjold, O. Stal, S. Thorstenson, P.-E. Jonsson, and G. Landberg Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer J. Clin. Oncol., July 20, 2005; 23(21): 4695 - 4704. [Abstract] [Full Text] [PDF]
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G. Arpino, H.L. Weiss, G.M. Clark, S.G. Hilsenbeck, and C.K. Osborne Hormone Receptor Status of a Contralateral Breast Cancer Is Independent of the Receptor Status of the First Primary in Patients Not Receiving Adjuvant Tamoxifen J. Clin. Oncol., July 20, 2005; 23(21): 4687 - 4694. [Abstract] [Full Text] [PDF]
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M. De Laurentiis, G. Arpino, E. Massarelli, A. Ruggiero, C. Carlomagno, F. Ciardiello, G. Tortora, D. D'Agostino, F. Caputo, G. Cancello, et al. A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer Clin. Cancer Res., July 1, 2005; 11(13): 4741 - 4748. [Abstract] [Full Text] [PDF]
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S. Tovey, B. Dunne, C. J. Witton, A. Forsyth, T. G. Cooke, and J. M.S. Bartlett Can Molecular Markers Predict When to Implement Treatment with Aromatase Inhibitors in Invasive Breast Cancer? Clin. Cancer Res., July 1, 2005; 11(13): 4835 - 4842. [Abstract] [Full Text] [PDF]
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A. Howell and A. M Wardley Overview of the impact of conventional systemic therapies on breast cancer Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S9 - S16. [Abstract] [Full Text] [PDF]
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B. W. O'Malley A Life-Long Search for the Molecular Pathways of Steroid Hormone Action Mol. Endocrinol., June 1, 2005; 19(6): 1402 - 1411. [Abstract] [Full Text] [PDF]
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R.-C. Wu, C. L. Smith, and B. W. O'Malley Transcriptional Regulation by Steroid Receptor Coactivator Phosphorylation Endocr. Rev., May 1, 2005; 26(3): 393 - 399. [Abstract] [Full Text] [PDF]
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J. Geisler and P. E. Lonning Aromatase Inhibition: Translation into a Successful Therapeutic Approach Clin. Cancer Res., April 15, 2005; 11(8): 2809 - 2821. [Abstract] [Full Text] [PDF]
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J. Baselga and C. L. Arteaga Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer J. Clin. Oncol., April 10, 2005; 23(11): 2445 - 2459. [Abstract] [Full Text] [PDF]
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M. C. Gutierrez, S. Detre, S. Johnston, S. K. Mohsin, J. Shou, D. C. Allred, R. Schiff, C. K. Osborne, and M. Dowsett Molecular Changes in Tamoxifen-Resistant Breast Cancer: Relationship Between Estrogen Receptor, HER-2, and p38 Mitogen-Activated Protein Kinase J. Clin. Oncol., April 10, 2005; 23(11): 2469 - 2476. [Abstract] [Full Text] [PDF]
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E. Myers, A. D.K. Hill, G. Kelly, E. W. McDermott, N. J. O'Higgins, Y. Buggy, and L. S. Young Associations and Interactions between Ets-1 and Ets-2 and Coregulatory Proteins, SRC-1, AIB1, and NCoR in Breast Cancer Clin. Cancer Res., March 15, 2005; 11(6): 2111 - 2122. [Abstract] [Full Text] [PDF]
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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]
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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]
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