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.
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 cancerpatients, we quantified expression of AIB1 and HER-2 in tumors from breast cancerpatients 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 cancerpatients 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.
Authors: Victoria Wargon; Marina Riggio; Sebastián Giulianelli; Gonzalo R Sequeira; Paola Rojas; María May; María L Polo; María A Gorostiaga; Britta Jacobsen; Alfredo Molinolo; Virginia Novaro; Claudia Lanari Journal: Int J Cancer Date: 2014-11-12 Impact factor: 7.396
Authors: Christopher D Chien; Alexander Kirilyuk; Jordan V Li; Wentao Zhang; Tyler Lahusen; Marcel O Schmidt; Annabell S Oh; Anton Wellstein; Anna T Riegel Journal: J Biol Chem Date: 2011-06-02 Impact factor: 5.157
Authors: Gladys Morrison; Xiaoyong Fu; Martin Shea; Sarmistha Nanda; Mario Giuliano; Tao Wang; Teresa Klinowska; C Kent Osborne; Mothaffar F Rimawi; Rachel Schiff Journal: Breast Cancer Res Treat Date: 2014-02-20 Impact factor: 4.872
Authors: Maria D Corte; Juan A Rodil; Julio Vázquez; Lucia García; Juan C Rodríguez; Miguel Bongera; José C Fernández; Luis O González; Ma Luz Lamelas; Maite Allende; José L García-Muñiz; Antonio Fueyo; Francisco J Vizoso Journal: J Cancer Res Clin Oncol Date: 2005-11-01 Impact factor: 4.553