Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells.

Free Radical Biology & Medicine
Suresh VeeramaniMing-Fong Lin

Abstract

Steroid hormones exhibit diverse biological activities. Despite intensive studies on steroid function at the genomic level, their nongenomic actions remain an enigma. In this study, we investigated the role of reactive oxygen species (ROS) in androgen-stimulated prostate cancer (PCa) cell proliferation. In androgen-treated PCa cells, increased cell growth and ROS production correlated with elevated p66Shc protein, an authentic oxidase. This growth stimulation was blocked by antioxidants. Further, elevated expression of p66Shc protein by cDNA transfection encoding wild-type protein, but not a redox-deficient (W134F) mutant, was associated with increased PCa cell proliferation. Conversely, knockdown of p66Shc expression by shRNA resulted in diminished cell growth. Increased p66Shc expression in PCa cells enhanced their tumorigenicity in xenograft animals. Importantly, p66Shc protein level is higher in clinical prostate adenocarcinomas than in adjacent noncancerous cells. Expression of redox-deficient p66Shc mutant protein abolished androgen-stimulated cell growth. In androgen-treated, H(2)O(2)-treated, and p66Shc cDNA-transfected PCa cells, cellular prostatic acid phosphatase, an authentic tyrosine phosphatase, was inactivated by...Continue Reading

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Citations

Dec 20, 2012·Molecular Endocrinology·Yan ShiDaniel E Frigo
Dec 20, 2014·European Journal of Clinical Investigation·Magdalena Lebiedzinska-ArciszewskaMariusz R Wieckowski
Mar 7, 2013·Free Radical Biology & Medicine·Amélie RebillardJosiane Cillard
Jan 8, 2014·Molecular Carcinogenesis·Sakthivel MuniyanMing-Fong Lin
Jul 12, 2019·Endocrine-related Cancer·Dannah R MillerMing-Fong Lin
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jiangyong YuJie Wang
Feb 21, 2018·Cellular Signalling·Matthew A IngersollMing-Fong Lin
Oct 17, 2020·BioMed Research International·Chenglin HanXunbo Jin

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