A detailed characterization of stepwise activation of the androgen receptor variant 7 in prostate cancer cells.

Abstract	Expression of the androgen receptor splice variant 7 (AR-V7) is frequently detected in castrate resistant prostate cancer and associated with resistance to AR-targeted therapies. While we have previously noted that homodimerization is required for the transcriptional activity of AR-V7 and that AR-V7 can also form heterodimers with the full-length AR (AR-FL), there are still many gaps of knowledge in AR-V7 stepwise activation. In the present study, we show that neither AR-V7 homodimerization nor AR-V7/AR-FL heterodimerization requires cofactors or DNA binding. AR-V7 can enter the nucleus as a monomer and drive a transcriptional program and DNA-damage repair as a homodimer. While forming a heterodimer with AR-FL to induce nuclear localization of unliganded AR-FL, AR-V7 does not need to interact with AR-FL to drive gene transcription or DNA-damage repair in prostate cancer cells that co-express AR-V7 and AR-FL. These data indicate that AR-V7 can function independently of its interaction with AR-FL in the true castrate state or "absence of ligand", providing support for the utility of targeting AR-V7 in improving outcomes of patients with castrate resistant prostate cancer.
Authors	Carlos M Roggero, Lianjin Jin, Subing Cao, Rajni Sonavane, Noa G Kopplin, Huy Q Ta, Dede N Ekoue, Michael Witwer, Shihong Ma, Hong Liu, Tianfang Ma, Daniel Gioeli, Ganesh V Raj, Yan Dong
Journal	Oncogene (Oncogene) Vol. 40 Issue 6 Pg. 1106-1117 (02 2021) ISSN: 1476-5594 [Electronic] England
PMID	33323969 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	AR protein, human DNA-Binding Proteins Protein Isoforms Receptors, Androgen
Topics	Alternative Splicing (genetics) Cell Line, Tumor Cell Nucleus (genetics) DNA Damage (genetics) DNA Repair (genetics) DNA-Binding Proteins (genetics) Gene Expression Regulation, Neoplastic (genetics) Humans Male Prostate (pathology) Prostatic Neoplasms (genetics, pathology) Protein Isoforms (genetics) Receptors, Androgen (genetics)

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