title: Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors.
abstract: We searched ERα cistromes of MCF-7 breast cancer cells for previously unrecognized ERα 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 ERα-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 ERα target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Malinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Jääskeläinen
authors.forename: Mikko
authors.initials: M
authors.lastname: Pelkonen
authors.forename: Sami
authors.initials: S
authors.lastname: Heikkinen
authors.forename: Sami
authors.initials: S
authors.lastname: Väisänen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Kaisa
authors.initials: K
authors.lastname: Nieminen
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D060787:Neoplasm Grading; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D004958:Estradiol; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; D018844:Cyclin-Dependent Kinases