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p53-dependent induction of heat shock protein 27 (HSP27) expression
1Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20852, USA.
Abstract:
Transcriptional activation of the p53 target genes plays a critical role in the cellular response to DNA damage, hypoxia, cellular stress and other signals regulating the cell cycle and apoptosis. The discovery of new p53 target genes continues to reveal novel mechanisms of action of this multifaceted protein. We used cDNA arrays to search for p53-regulated genes in prostate cancer cells. In this report, we describe robust induction of heat shock protein 27 (hsp27) in prostate cancer cells (DU145, LNCaP, PC3) following wild-type p53 expression from an adenoviral p53 expression vector (AdWTp53). A mutant p53 (R175H)-containing adenoviral expression vector did not induce hsp27. hsp27 expression was not altered in prostate cancer cells following expression of cyclin-dependent kinase inhibitors: p21(waf1/cip1) and p27(kip1) from adenoviral expression vectors. Treatment of cells with staurosporine, an apoptosis-inducing agent, did no affect hsp27 expression. These observations provide evidence that induction of hsp27 expression was wild-type p53-specific and was not due to non-specific effects of cell growth arrest and/or apoptosis. Previous studies and the experiment reported here show induction of hsp27 expression in response to androgen ablation, a physiological state that induces apoptosis in prostatic epithelial cells. The nature of p53 and hsp27 interactions in the regulation of apoptosis and/or cell growth needs to be further defined.
Insights
Wild-type p53 specifically induces heat shock protein 27 (hsp27) in prostate cancer cells, independent of cell cycle arrest or apoptosis. This finding reveals a new p53 target gene with potential roles in cancer progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- The p53 tumor suppressor protein regulates critical cellular processes including cell cycle arrest and apoptosis.
- Identifying novel p53 target genes is crucial for understanding its multifaceted roles in cellular responses.
- Prostate cancer cells are a relevant model for studying p53-mediated gene regulation.
Purpose of the Study:
- To identify novel p53 target genes in prostate cancer cells using cDNA arrays.
- To investigate the specific induction of heat shock protein 27 (hsp27) by wild-type p53.
- To determine if hsp27 induction is specific to wild-type p53 and not a general response to cellular stress.
Main Methods:
- Utilized cDNA arrays to screen for p53-regulated genes in prostate cancer cell lines (DU145, LNCaP, PC3).
- Employed adenoviral vectors to express wild-type p53 (AdWTp53) and a mutant p53 (R175H).
- Assessed hsp27 expression following p53 expression and treatment with apoptosis-inducing agents (staurosporine) or cell cycle inhibitors (p21, p27).
Main Results:
- Robust induction of heat shock protein 27 (hsp27) was observed in prostate cancer cells upon expression of wild-type p53.
- A mutant p53 (R175H) did not induce hsp27 expression, indicating specificity.
- hsp27 expression remained unaltered following expression of p21 or p27, and was unaffected by staurosporine treatment.
- hsp27 induction by wild-type p53 was confirmed to be specific and not a consequence of cell cycle arrest or apoptosis.
Conclusions:
- Wild-type p53 specifically induces hsp27 expression in prostate cancer cells.
- hsp27 is a novel p53 target gene, and its induction is independent of cell cycle arrest or apoptosis.
- Further research is needed to elucidate the precise role of p53 and hsp27 interaction in regulating apoptosis and cell growth in prostate cancer.