A molecular analysis provides novel insights into androgen receptor signalling in breast cancer

PloS One
Jatin MehtaSunita Saxena

Abstract

Androgen Receptor (AR) is an essential transcription factor for the development of secondary sex characteristics, spermatogenesis and carcinogenesis. Recently AR has been implicated in the development and progression of breast and prostate cancers. Although some of the functions of the AR are known but the mechanistic details of these divergent processes are still not clear. Therefore understanding the regulatory mechanisms of the functioning of the AR in ER-/AR+ breast cancer will provide many novel targets for the purpose of therapeutic intervention. Using bioinformatics tools, we have identified 75 AR targets having prominent roles in cell cycle, apoptosis and metabolism. Herein, we validated 10 genes as AR targets by studying the regulation of these genes in MDA-MB-453 cell line on stimulation by androgens like 5α-dihydrotestosterone (DHT), using RT-qPCR and ChIP assay. It was observed that all the identified genes involved in cell cycle except MAD1L1 were found to be up regulated whereas expression of apoptosis related genes was decreased in response to DHT treatment. We performed an exhaustive, rigid-body docking between individual ARE and DNA binding domain (DBD) of the AR protein and it was found that novel residues K56...Continue Reading

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Apr 19, 2016·DNA Repair·Satya NarayanRobert A Hromas
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Sep 21, 2017·Frontiers in Pharmacology·Kaushik ChowdhuryChandi C Mandal

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Methods Mentioned

BETA
FCS
ChIP
PCR
Immunoprecipitation
immunoprecipitations
scraping
flow cytometry
FACS

Clinical Trials Mentioned

NCT00468715

Software Mentioned

MUSCLE
3D
DOT
VMD
ClustalW
msms
primer
APBS
TFSEARCH
Sigma Plot

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