ERK regulates calpain 2-induced androgen receptor proteolysis in CWR22 relapsed prostate tumor cell lines.

The Journal of Biological Chemistry
Honglin ChenMaria Mudryj

Abstract

Androgen ablation therapy is effective in treating androgen-dependent prostate tumors; however, tumors that can proliferate in castrate levels of androgen eventually arise. We previously reported that in CWR22Rv1 (Rv1) cells, the protease calpain 2 can cleave the androgen receptor (AR) into a constitutively active approximately 80,000 low molecular weight (LMW) form. In this study, we further dissect the mechanisms that produce the AR LMW forms using Rv1 cells and the related CWR22-R1 (R1) cells. The 39-amino acid insertional mutation in the Rv1-AR (E3DM-AR) sensitizes this AR to calpain 2 proteolysis. R1 cells encode the same AR molecule as the parental CWR22 xenograft. Using calpain 2 small interfering RNA and calpeptin, we find that calpain 2 plays a role in the generation of the LMW-AR in R1 cells. Furthermore, LMW-AR expression is regulated by the activation of calpain 2 by ERK 1 and 2. Inhibition of ERK phosphorylation or small interfering RNA-mediated decrease of ERK expression reduces LMW-AR levels in R1 cells. Conversely, activation of the MAPK pathway results in increased ERK phosphorylation and increased levels of LMW-AR. Finally, analyses of human tumor samples found that LMW-AR levels are higher in tumors that have...Continue Reading

References

Jul 1, 1991·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J A Ruizeveld de WinterT H van der Kwast
Sep 24, 1999·The Journal of Urology·D T PriceL M Luttrell
Nov 30, 2000·Nucleic Acids Research·D C Porter, K Keyomarsi
Nov 24, 2001·Journal of Molecular Endocrinology·C W GregoryE M Wilson
Apr 5, 2002·Molecular Cell·Yongfeng ShangMyles Brown
Feb 8, 2003·Molecular and Cellular Endocrinology·Cor A BerrevoetsAlbert O Brinkmann
Feb 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maggie C LouieHong-Wu Chen
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Nov 18, 2003·International Journal of Cancer. Journal International Du Cancer·Jocelyn CéralineJean-Pierre Bergerat
Jan 2, 2004·Nature Medicine·Charlie D ChenCharles L Sawyers
Feb 3, 2004·Journal of Cellular Biochemistry·Mary-Ellen Taplin, Steven P Balk
Feb 28, 2004·The Journal of Biological Chemistry·Peter TompaPeter Friedrich
Feb 15, 2005·The Journal of Biological Chemistry·Hannah WingateKhandan Keyomarsi
Aug 30, 2008·Journal of Cellular Physiology·Huanjie YangQ Ping Dou

❮ Previous
Next ❯

Citations

Jul 13, 2011·Cellular and Molecular Life Sciences : CMLS·Simon Haile, Marianne D Sadar
Feb 8, 2013·Carcinogenesis·Weiwei GaoXiao-kun Zhang
Jul 23, 2011·Endocrine-related Cancer·Scott M Dehm, Donald J Tindall
Dec 4, 2013·International Journal of Oncology·Tiancheng LiuClifford E Berkman
Jul 19, 2013·Hormones & Cancer·Maria Mudryj, Clifford G Tepper
Apr 21, 2011·Journal of Cellular Physiology·Arun SivanandamG Prem-Veer Reddy
Jul 25, 2015·Cell Research·Wu-Chang ZhangSheng-Zhong Duan
Feb 11, 2015·Nature Reviews. Urology·Ji LuDonald J Tindall
Sep 9, 2016·Endocrine-related Cancer·Paramita M Ghosh
Jul 28, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Katarzyna StarskaMagdalena Bryś
Jan 29, 2017·Biochimica Et Biophysica Acta. General Subjects·Ana SaavedraEsther Pérez-Navarro
Aug 16, 2017·Endocrine-related Cancer·Takuma UoCynthia C Sprenger
Apr 22, 2011·Nature Reviews. Cancer·Sarah J StorrStewart G Martin
Dec 9, 2010·International Journal of Cancer. Journal International Du Cancer·Sarah J StorrStewart G Martin
May 6, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jieping HuTing Sun
Sep 7, 2018·Frontiers in Molecular Neuroscience·Li WanYun Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.