|Estrogen receptor alpha-coupled Bmi1 regulation pathway in breast cancer and its clinical implications|
|Wang, Huali1; Liu, Haijing1; Li, Xin1; Zhao, Jing1; Zhang, Hong1; Mao, Jingzhuo1; Zou, Yongxin1; Zhang, Hong2; Zhang, Shuang2; Hou, Wei1; Hou, Lin1; McNutt, Michael A.1; Zhang, Bo1|
|关键词||Bmi1 Estrogen receptor alpha p16(INK4a) Cyclin D1 Breast cancer|
|WOS标题词||Science & Technology|
|关键词[WOS]||TARGET GENE ; STEM-CELLS ; CYCLIN D1 ; ENDOCRINE THERAPY ; SELF-RENEWAL ; EXPRESSION ; REPRESSION ; CARCINOMA ; ELEMENT ; PROLIFERATION|
Background: Bmi1 has been identified as an important regulator in breast cancer, but its relationship with other signaling molecules such as ER alpha and HER2 is undetermined.
Methods: The expression of Bmi1 and its correlation with ER alpha, PR, Ki-67, HER2, p16(INK4a), cyclin D1 and pRB was evaluated by immunohistochemistry in a collection of 92 cases of breast cancer and statistically analyzed. Stimulation of Bmi1 expression by ER alpha or 17 beta-estradiol (E2) was analyzed in cell lines including MCF-7, MDA-MB-231, ER alpha-restored MDA-MB-231 and ER alpha-knockdown MCF-7 cells. Luciferase reporter and chromatin immunoprecipitation assays were also performed.
Results: Immunostaining revealed strong correlation of Bmi1 and ER alpha expression status in breast cancer. Expression of Bmi1 was stimulated by 17 beta-estradiol in ER alpha-positive MCF-7 cells but not in ER alpha-negative MDA-MB-231 cells, while the expression of Bmi1 did not alter expression of ER alpha. As expected, stimulation of Bmi1 expression could also be achieved in ER alpha-restored MDA-MB-231 cells, and at the same time depletion of ER alpha decreased expression of Bmi1. The proximal promoter region of Bmi1 was transcriptionally activated with co-transfection of ER alpha in luciferase assays, and the interaction of the Bmi1 promoter with ER alpha was confirmed by chromatin immunoprecipitation. Moreover, in breast cancer tissues activation of the ER alpha-coupled Bmi1 pathway generally correlated with high levels of cyclin D1, while loss of its activity resulted in aberrant expression of p16(INK4a) and a high Ki-67 index, which implied a more aggressive phenotype of breast cancer.
Conclusions: Expression of Bmi1 is influenced by ER alpha, and the activity of the ER alpha-coupled Bmi1 signature impacts p16(INK4a) and cyclin D1 status and thus correlates with the tumor molecular subtype and biologic behavior. This demonstrates the important role which is played by ER alpha-coupled Bmi1 in human breast cancer.
|资助机构||National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China|
2.Peking Univ, Hosp 1, Dept Pathol, Beijing 100034, Peoples R China
|Wang, Huali,Liu, Haijing,Li, Xin,et al. Estrogen receptor alpha-coupled Bmi1 regulation pathway in breast cancer and its clinical implications[J]. BMC CANCER,2014,14(0).|
|APA||Wang, Huali.,Liu, Haijing.,Li, Xin.,Zhao, Jing.,Zhang, Hong.,...&Zhang, Bo.(2014).Estrogen receptor alpha-coupled Bmi1 regulation pathway in breast cancer and its clinical implications.BMC CANCER,14(0).|
|MLA||Wang, Huali,et al."Estrogen receptor alpha-coupled Bmi1 regulation pathway in breast cancer and its clinical implications".BMC CANCER 14.0(2014).|
|Estrogen receptor al（2966KB）||期刊论文||出版稿||开放获取||CC BY-NC-SA||浏览 请求全文|