ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors.

Neoplasia : an International Journal for Oncology Research
Shinichi YamashitaChawnshang Chang

Abstract

Early studies suggested androgen receptor (AR) splice variants might contribute to the progression of prostate cancer (PCa) into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR) and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown) cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrate...Continue Reading

Citations

Apr 12, 2013·International Journal of Cancer. Journal International Du Cancer·Yang ZhanYan Dong
Jul 19, 2013·Hormones & Cancer·Maria Mudryj, Clifford G Tepper
May 2, 2014·Journal of Molecular Endocrinology·Momoe ItsumiSeiji Naito
Oct 23, 2015·BioMed Research International·Ruibao ChenZhangqun Ye
Jan 16, 2016·The Journal of Endocrinology·Chiung-Kuei HuangChawnshang Chang
Sep 27, 2016·International Journal of Cancer. Journal International Du Cancer·Junjie XuChawnshang Chang
Feb 11, 2015·Nature Reviews. Urology·Ji LuDonald J Tindall
Jun 4, 2014·Expert Opinion on Pharmacotherapy·Zoran Culig
Aug 16, 2017·Endocrine-related Cancer·Takuma UoCynthia C Sprenger
Sep 5, 2018·Scientific Reports·Alicia de Las PozasCarlos Perez-Stable
May 10, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Na ShangWei Qiu
Mar 19, 2014·Endocrine-related Cancer·Christine HelsenFrank Claessens
Jul 23, 2014·Hormones & Cancer·Mary NakazawaJun Luo
Nov 26, 2015·Clinical Investigation·Kouji IzumiChawnshang Chang
Sep 4, 2015·BMC Medicine·Thenappan ChandrasekarChristopher P Evans
Jun 19, 2018·Frontiers in Oncology·Alexandra Vander ArkXiaohong Li
Jun 14, 2019·Frontiers in Chemistry·Giovanni L Beretta, Nadia Zaffaroni
Mar 25, 2019·Journal of Cellular and Molecular Medicine·Hongyan XiaYan Dong
Aug 22, 2012·International Journal of Cancer. Journal International Du Cancer·Bo CaoYan Dong
Sep 4, 2015·The Journal of Biological Chemistry·Vidyavathi ReddySahn-Ho Kim
Jul 23, 2016·Nature Reviews. Drug Discovery·Timothy A YapJohann S de Bono
Oct 22, 2016·Endocrine-related Cancer·Subing CaoYan Dong
Jul 20, 2017·International Journal of Cancer. Journal International Du Cancer·Bin WangJer-Tsong Hsieh
Feb 9, 2018·Expert Opinion on Therapeutic Targets·Takuma UoCynthia C Sprenger
Feb 28, 2019·Endocrinology·Mavis A A TenkorangRebecca L Cunningham
Nov 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hsiu-Ping LinWen-Jye Lin
Mar 2, 2016·Expert Opinion on Therapeutic Targets·M T Schweizer, S R Plymate

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