Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors

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• 作者：Marjo Malinen^a ; Tiina Jä ; ä ; skelä ; inen^a ; ^b ; Mikko Pelkonen^c ; ^d ; Sami Heikkinen^a ; Sami Vä ; isä ; nen^a ; Veli-Matti Kosma^c ; ^d ; Kaisa Nieminen^c ; ^d ; Arto Mannermaa^c ; ^d ; Jorma J. Palvimo^a ; ^{jorma.palvimo@uef.fi}
• 关键词：Estrogen receptor (ER) ¦Á ; 17¦Â-estradiol ; Cell growth ; Breast cancer ; PIM-1
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2013
• 出版时间：30 January, 2013
• 年：2013
• 卷：365
• 期：2
• 页码：270-276
• 全文大小：462 K

文摘

We searched ER¦Á cistromes of MCF-7 breast cancer cells for previously unrecognized ER¦Á 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¦Á-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¦Á target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis.