p53-dependent induction of heat shock protein 27 (hsp27) expression

Transcriptional activation of the p53 target genes plays a critical role in the cellular response to DNA damage, hypoxia, cellular stress and other si gnals regulating the cell cycle and apoptosis. The discovery of new p53 tar get genes continues to reveal novel mechanisms of action of this multifacet ed protein. We used cDNA arrays to search for p53-regulated genes in prosta te cancer cells. In this report, we describe robust induction of heat shock protein 27 (hsp27) in prostate cancer cells (DU145, LNCaP, PC3) following wildtype p53 expression from an adenoviral p53 expression vector (AdWTp53). A mutant p53 (R175H)-containing adenoviral expression vector did not induc e hsp27. hsp27 expression was not altered in prostate cancer cells followin g expression of cyclin-dependent kinase inhibitors: p21(waf1/cip1) and p27( kip1) from adenoviral expression vectors. Treatment of cells with staurospo rine, an apoptosis-inducing agent, did no affect hsp27 expression. These ob servations provide evidence that induction of hsp27 expression was wild-typ e p53-specific and was not due to non-specific effects of cell growth arres t and/or apoptosis. Previous studies and the experiment reported here show induction of hsp27 expression in response to androgen ablation, a physiolog ical state that induces apoptosis in prostatic epithelial cells. The nature of p53 and hsp27 interactions in the regulation of apoptosis and/or cell g rowth needs to be further defined. Int. J. Cancer 88:191-194, 2000. (C) 200 0 Wiley-Liss, Inc.