Coassociation of Estrogen Receptor and p160 Proteins Predicts Resistance to Endocrine Treatment; SRC-1 is an Independent Predictor of Breast Cancer Recurrence
Coassociation of Estrogen Receptor and p160 Proteins Predicts Resistance to Endocrine Treatment; SRC-1 is an Independent Predictor of Breast Cancer Recurrence
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DOI：
10.1158/1078-0432.ccr-08-1649
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发表时间：
2009-03-15
影响因子：
11.5
通讯作者：
Young, Leonie S.
中科院分区：
文献类型：
--
作者：
Redmond, Aisling M.;Bane, Fiona T.;Young, Leonie S.
目的：本研究调查了p160共激活因子AIB 1和SRC-1的作用，以及它们与雌激素受体的相互作用，在内分泌治疗耐药性的发展中的作用。p160和雌激素受体的表达，以及它们之间的相互作用，通过免疫组织化学和定量联合免疫荧光显微镜分析，使用细胞系，原代乳腺肿瘤细胞培养物，结果：与内分泌敏感的MCF-7细胞相比，用他莫昔芬处理后，LY 2内分泌抵抗细胞系中p160和雌激素受体α的共结合增加。在原代培养物中，雌激素处理后，与雌激素受体a相关的辅激活因子增加，但与他莫昔芬分离明显。组织微阵列的免疫组织化学染色显示，SRC-1是接受他莫昔芬辅助治疗和未治疗患者无病生存期（DFS）降低的强预测因子（分别为P < 0.0001和P = 0.0111）。使用考克斯比例风险模型，SRC-1的风险比为2.12。与所有其他患者相比，共表达AIB 1和人表皮生长因子受体2的内分泌治疗患者的DFS显著缩短（P = 0.03）。患者组织微阵列的定量共相关分析显示，与未复发的患者相比，复发患者中AIB 1和SRC-1与雌激素受体a的共定位显著更强。（分别为P = 0.026和P = 0.00001）。结论：SRC-1是DFS降低的强独立预测因子，而p160蛋白与雌激素受体a的相互作用可以预测患者对内分泌治疗的反应。
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 a 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 a 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 a can predict the response of patients to endocrine treatment.