BCAS2 Enhances Carcinogenic Effects of Estrogen Receptor Alpha in Breast Cancer Cells.

International Journal of Molecular Sciences
Ángel Salmerón-HernándezElizabeth Langley

Abstract

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promo...Continue Reading

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Citations

Mar 27, 2020·OncoTargets and Therapy·Yanfang LiuJing Yao
Aug 6, 2020·International Journal of Environmental Research and Public Health·Alan A ArslanJoan Reibman
Jun 20, 2021·Molecular and Cellular Endocrinology·Zixiang WangZhaojian Liu
Jan 1, 2022·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiaqi ZhangLei Li

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Methods Mentioned

BETA
histone acetylation
ubiquitination
two-hybrid
pull-down
ChIP
transfection
transfections
Immunoprecipitation
PCR

Software Mentioned

Graph Pad Prism
Basic Local Alignment Search Tool ( BLAST )

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