期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 365, 期 2, 页码 270-276出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.10.028
关键词
Estrogen receptor (ER) alpha; 17 beta-estradiol; Cell growth; Breast cancer; PIM-1
资金
- Academy of Finland
- Juselius Foundation
- (EVO) of Kuopio University Hospital
- Kuopio Northern Savo Cancer Society
- Cancer Society of Finland
- University of Eastern Finland
We searched ER alpha cistromes of MCF-7 breast cancer cells for previously unrecognized ER alpha targets and identified proto-oncogene PIM-1 as a novel potential target gene. We show that the expression of PIM-1 is induced in response to estradiol in MCF-7 cells and that the induction is mediated by ER alpha-regulated enhancers located distally upstream from the gene. In keeping with the growth-promoting role of the PIM-1, depletion of the PIM-1 attenuated the proliferation of the MCF-7 cells, which was paralleled with up-regulation of cyclin-dependent protein kinase inhibitor CDKN1A and CDKN2B expression. Analysis of PIM-1 expression between invasive breast tumors and benign breast tissue samples showed that elevated PIM-1 expression is associated with malignancy and a higher tumor grade. In sum, identification of PIM-1 as an ER alpha target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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