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Title: Research resource: global identification of estrogen receptor * target genes in triple negative breast cancer cells.

Authors: Shanle, Erin K; Zhao, Zibo; Hawse, John; Wisinski, Kari; Keles, Sunduz; Yuan, Ming; Xu, Wei

Published In Mol Endocrinol, (2013 Oct)

Abstract: Breast cancers that are negative for estrogen receptor * (ER*), progesterone receptor, and human epidermal growth factor receptor 2 are known as triple-negative breast cancers (TNBC). TNBCs are associated with an overall poor prognosis because they lack expression of therapeutic targets like ER* and are biologically more aggressive. A second estrogen receptor, ER*, has been found to be expressed in 50% to 90% of ER*-negative breast cancers, and ER* expression in TNBCs has been shown to correlate with improved disease-free survival and good prognosis. To elucidate the role of ER* in regulating gene expression and cell proliferation in TNBC cells, the TNBC cell line MDA-MB-468 was engineered with inducible expression of full-length ER*. In culture, ER* expression inhibited cell growth by inducing a G1 cell cycle arrest, which was further enhanced by 17*-estradiol treatment. In xenografts, ER* expression also inhibited tumor formation and growth, and 17*-estradiol treatment resulted in rapid tumor regression. Furthermore, genomic RNA sequencing identified both ligand-dependent and -independent ER* target genes, some of which were also regulated by ER* in other TNBC cell lines and correlated with ER* expression in a cohort of TNBCs from the Cancer Genome Atlas Network. ER* target genes were enriched in genes that regulate cell death and survival, cell movement, cell development, and growth and proliferation, as well as genes involved in the Wnt/*-catenin and the G1/S cell cycle phase checkpoint pathways. In addition to confirming the anti-proliferative effects of ER* in TNBC cells, these data provide a comprehensive resource of ER* target genes and suggest that ER* may be targeted with ligands that can stimulate its growth inhibitory effects.

PubMed ID: 23979844 Exiting the NIEHS site

MeSH Terms: Animals; Cell Line, Tumor; Cell Proliferation; Estradiol/physiology; Estrogen Receptor beta/physiology*; Female; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic*; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Transcriptome*; Triple Negative Breast Neoplasms/genetics; Triple Negative Breast Neoplasms/metabolism*

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