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

Marjo Malinen; Tiina Jääskeläinen; Mikko Pelkonen; Sami Heikkinen; Sami Väisänen; Veli-Matti Kosma; Kaisa Nieminen; Arto Mannermaa; Jorma J Palvimo

doi:10.1016/j.mce.2012.10.028

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

Mol Cell Endocrinol. 2013 Jan 30;365(2):270-6. doi: 10.1016/j.mce.2012.10.028. Epub 2012 Nov 6.

Authors

Marjo Malinen¹, Tiina Jääskeläinen, Mikko Pelkonen, Sami Heikkinen, Sami Väisänen, Veli-Matti Kosma, Kaisa Nieminen, Arto Mannermaa, Jorma J Palvimo

Affiliation

¹ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

PMID: 23142699
DOI: 10.1016/j.mce.2012.10.028

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / metabolism*
Breast Neoplasms / mortality
Breast Neoplasms / pathology
Carcinoma, Ductal, Breast / metabolism*
Carcinoma, Ductal, Breast / mortality
Carcinoma, Ductal, Breast / pathology
Carcinoma, Lobular / metabolism*
Carcinoma, Lobular / mortality
Carcinoma, Lobular / pathology
Case-Control Studies
Cyclin-Dependent Kinases / genetics
Cyclin-Dependent Kinases / metabolism
Estradiol / physiology
Estrogen Receptor alpha / physiology*
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
MCF-7 Cells
Neoplasm Grading
Proto-Oncogene Mas
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
Proto-Oncogene Proteins c-pim-1 / genetics
Proto-Oncogene Proteins c-pim-1 / metabolism*
RNA, Small Interfering / genetics

Substances

ESR1 protein, human
Estrogen Receptor alpha
MAS1 protein, human
MYC protein, human
Proto-Oncogene Mas
Proto-Oncogene Proteins c-myc
RNA, Small Interfering
Estradiol
PIM1 protein, human
Proto-Oncogene Proteins c-pim-1
Cyclin-Dependent Kinases