The relation of the anti-cancer drug resistance and heat shock protein 60 expression

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The expression of the 60-kDa heat-shock protein (HSP60) varies markedly among pateints with ovarian carcinoma, and high-level expression predicts poor survival in such patients treated with cisplatin (DDP)-containing chemotherapy programs. I investigated the expression of HSP60 in human ovarian carcinoma 2008 cells and an 11-fold DDP-resistant subline 2008/C13<@D1**@>D15.25. Heating for 2 h at 44ﾟC produced a 2.7(]SY.+-。[)0.16-fold increase (mean (]SY.+-。[)SD) that was maximal at 4 h after the start of heat exposure. Exposure to an IC50 concentration of DDP for 1 h induced a 1.8(]SY.+-。[)0.03-fold increase in hsp60 expression. The opposite was true for cadmimum and zinc, both of which induced increases in metallothionein IIA but not in the hsp60 message. 2008/C13<@D1**@>D15.25 cells cnstitutively overexpressed hsp60 mRNA by 1.7(]SY.+-。[)0.16 orders of magmitude and contained a 3.8(]SY.+-。[)0.45-fold higher level of HSP60as detected by immunocytochemical satining. 2008/C13<@D1**@>D15.25 cells showed 1.2-fold cross-resistance to thermal killing. Expression of hsp60 was markedly reducedin 2008 xenografts as compared with 2008 cells growing in-vitro ; however, neither serum starvation nor refeeding altered the message level. Exposure to a variety of growth factor and drug treatments known to alter the DDP sensitivity of2008 cells, including epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, buthionine sulfoximine, ouabain, and forskolin, did not alter hsp60 expression. These results suggest a role for HSP60 in mediating resistance to both DDP and hyperthermia but indicate that the hsp60 mRNA levels are not regulated by the factors listed above.