BACKGROUND. Resistance to apoptosis remains a significant problem in the tr
eatment of prostate cancer. Heat-shock proteins (HSP) have been correlated
with tumor progression. The role of HSP in prostate cancer resistance to ap
optosis is unknown.
METHODS. PC-3 and LNCaP prostate cancer cells were heat-shocked and then tr
eated with or without diethyl-maleate, etoposide, cycloheximide, or 3 Gray
irradiation. Percent apoptosis was assessed by propidium iodide DNA incorpo
ration. Protein was also extracted for analysis by SDS-PAGE Western blottin
g.
RESULTS. Western blotting confirmed an increase in HSP 27 and 72. These cel
ls were resistant to both chemical- and radiation-induced apoptosis. Cycloh
eximide and specific oligonucleotides to HSP 72 blocked the increased expre
ssion of HSP 72 and the resistance to apoptosis. Mcl-1, Bcl-2, Bcl-X-L, and
glutathione-S-transferase (GST) expression were increased in a time-depend
ent manner after heat shock.
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. (C) 2000 Wiley-Liss, Inc.