The expression of the 60-kDa
heat-shock protein (HSP60) varies markedly among patients with ovarian
carcinoma, and high-level expression predicts poor survival in such patients treated with
cisplatin (DDP)-containing
chemotherapy programs. We investigated the expression of HSP60 in human ovarian
carcinoma 2008 cells and an 11-fold DDP-resistant subline 2008/C13*5.25. Heating for 2 h at 44 degrees C produced a 2.7 +/- 0.16-fold increase (mean +/- 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 +/- 0.03-fold increase in hsp60 expression. The opposite was true for
cadmium and
zinc, both of which induced increases in
metallothionein IIA but not in the hsp60 message. 2008/C13*5.25 cells constitutively over-expressed hsp60
mRNA by 1.7 +/- 0.16 orders of magnitude and contained a 3.8 +/- 0.45-fold higher level of HSP60 as detected by immunocytochemical staining. 2008/C13*5.25 cells showed 1.2-fold cross-resistance to thermal killing. Expression of hsp60 was markedly reduced in 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 factors and
drug treatments known to alter the DDP sensitivity of 2008 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.