PMID: 11606392Oct 19, 2001Paper

Overexpressed androgen receptor linked to p21WAF1 silencing may be responsible for androgen independence and resistance to apoptosis of a prostate cancer cell line

Cancer Research
Longgui G WangAnna C Ferrari

Abstract

An androgen-independent (AI) prostate cancer cell line, derived recently from an LNCaP cell line maintained in androgen-poor conditions, has properties resembling a subgroup of advanced prostate cancers in that it has an overexpressed androgen receptor (AR), undetectable levels of p21WAF1 and prostate-specific antigen, and is resistant to apoptosis. The loss of prostate-specific antigen expression but not the p21WAF1 is attributable to gene silencing by hypermethylation. The high AR and undetectable p21WAF1 of AI cells, and lower AR but highly expressed p21WAF1 of androgen-dependent parental LNCaP cells, suggest a possibility of a functional link between these two proteins. Therefore, we examined the impact the modulation of AR will have on the expression of p21WAF1. Treatment of androgen-dependent cells with an androgen agonist, R1881, increased the AR protein level, whereas it simultaneously reduced the endogenous p21WAF1-protein 8-fold and the activity of a transiently transfected p21-promoter-reporter 10-fold. The down-regulation of p21WAF1 promoter appeared to be ARE mediated, dependent on AR, and not cell-type specific. Furthermore, a reduction of the AR level in AI cells by AR-antisense oligonucleotide increased the p21W...Continue Reading

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