PURPOSE: This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. EXPERIMENTAL DESIGN: The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. RESULTS: Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). CONCLUSIONS: SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.
PURPOSE: This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. EXPERIMENTAL DESIGN: The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. RESULTS: Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with humanepidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). CONCLUSIONS:SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.
Authors: Damian McCartan; Jarlath C Bolger; Aílis Fagan; Christopher Byrne; Yuan Hao; Li Qin; Marie McIlroy; Jianming Xu; Arnold D Hill; Peadar Ó Gaora; Leonie S Young Journal: Cancer Res Date: 2011-11-09 Impact factor: 12.701
Authors: Ekaterina V Kalashnikova; Alexey S Revenko; Abigael T Gemo; Nicolas P Andrews; Clifford G Tepper; June X Zou; Robert D Cardiff; Alexander D Borowsky; Hong-Wu Chen Journal: Cancer Res Date: 2010-09-23 Impact factor: 12.701
Authors: Li Qin; Ye-Lin Wu; Michael J Toneff; Dabing Li; Lan Liao; Xiuhua Gao; Fiona T Bane; Jean C-Y Tien; Yixiang Xu; Zhen Feng; Zhihui Yang; Yan Xu; Sarah M Theissen; Yi Li; Leonie Young; Jianming Xu Journal: Cancer Res Date: 2014-04-25 Impact factor: 12.701
Authors: Ryan J Hartmaier; Sandrine Tchatchou; Alexandra S Richter; Jay Wang; Sean E McGuire; Todd C Skaar; Jimmy M Rae; Kari Hemminki; Christian Sutter; Nina Ditsch; Peter Bugert; Bernhard H F Weber; Dieter Niederacher; Norbert Arnold; Raymonda Varon-Mateeva; Barbara Wappenschmidt; Rita K Schmutzler; Alfons Meindl; Claus R Bartram; Barbara Burwinkel; Steffi Oesterreich Journal: BMC Cancer Date: 2009-12-14 Impact factor: 4.430