Heat‐shock proteins inhibit induction of prostate cancer cell apoptosis

Abstract

BACKGROUND Resistance to apoptosis remains a significant problem in the treatment of prostate cancer. Heat‐shock proteins (HSP) have been correlated with tumor progression. The role of HSP in prostate cancer resistance to apoptosis is unknown. METHODS PC‐3 and LNCaP prostate cancer cells were heat‐shocked and then treated with or without diethyl‐maleate, etoposide, cycloheximide, or 3 Gray irradiation. Percent apoptosis was assessed by propidium iodide DNA incorporation. Protein was also extracted for analysis by SDS‐PAGE Western blotting. RESULTS Western blotting confirmed an increase in HSP 27 and 72. These cells were resistant to both chemical‐ and radiation‐induced apoptosis. Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased expression of HSP 72 and the resistance to apoptosis. Mcl‐1, Bcl‐2, Bcl‐XL, and glutathione‐S‐transferase (GST) expression were increased in a time‐dependent manner after heat shocke. CONCLUSIONS This study demonstrates that HSP expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines, which may be mediated by the production of survival factors. Prostate 45:58–65, 2000. © 2000 Wiley‐Liss, Inc.

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

“…phosphorylated Hsp-27 with the cytochrome c/Apaf-1/dATP complex, the Fas-adaptor FADD down-regulates the procaspase 9-dependent apoptotic pathway (Gibbons et al, 2000;Jolly and Morimoto, 2000;Charette et al, 2001). In the prostate, downregulation of apoptosis is associated with elevated levels of Hsp-27, such that PC-3 and LNCaP cells become resistant to both chemicaland radiation-induced apoptosis (Gibbons et al, 2000;Jolly and Morimoto, 2000).…”

“…In the prostate, downregulation of apoptosis is associated with elevated levels of Hsp-27, such that PC-3 and LNCaP cells become resistant to both chemicaland radiation-induced apoptosis (Gibbons et al, 2000;Jolly and Morimoto, 2000). In non-malignant cells Hsp-27 is phosphorylated by MAP kinase p38 (Rouse et al, 1994;, thus maintaining cellular homeostasis and integrity.…”

A potential role of heat shock proteins and nicotinamide N‐methyl transferase in predicting response to radiation in bladder cancer

“…Thus, it is not unlikely that upregulation will occur in response to radiation and result in radioresistance as the case is with HSP25. Gibbons et al 17 reported a decrease in the rate of apoptosis in irradiated prostate cell lines following initial induction of HSP (HSP27 and HSP72) and suggested that HSP expression provided protection against radiation-induced apoptosis. It seems reasonable to propose that levels of HSP27 are related to radiation response and might be a candidate target to predict the effect of radiotherapy.…”

Implication of PI3K-dependent HSP27 and p53 expression in mild heat shock-triggered switch of metabolic stress-induced necrosis to apoptosis in A549 cells

“…HSPs assist appropriate folding, assembly of newly synthesized polypeptides, and help intracellular trafficking of proteins in normal cells (22), and protect cells against stressful stimuli (23,24), and participate in the modulation of several apoptotic processes (25). They are generally found at elevated levels in various tumors including breast, prostate, colon and liver carcinoma, and their expression often correlates with increased cell proliferation and poor response to chemotherapy (26,27), thus, inhibition of HSPs has been suggested to be a potential target of anti-cancer therapy (28). Besides the anti-apoptotic role of HSPs, however, recent studies have indicated that HSPs are also involved in tumor immunogenicity and antigen presentation in ovarian carcinoma, melanoma, and osteosarcoma (29,30).…”