E. Kimura et al., REGULATION OF HSP60 MESSENGER-RNA EXPRESSION IN A HUMAN OVARIAN-CARCINOMA CELL-LINE, Cancer chemotherapy and pharmacology, 32(4), 1993, pp. 279-285
The expression of the 60-kDa heat-shock protein (HSP60) varies markedl
y among patients with ovarian carcinoma, and high-level expression pre
dicts poor survival in such patients treated with cisplatin (DDP)-cont
aining chemotherapy programs. We investigated the expression of HSP60
in human ovarian carcinoma 2008 cells and an 11-fold DDP-resistant sub
line 2008/C135.25. 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 st
art 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 opposit
e was true for cadmium and zinc, both of which induced increases in me
tallothionein II(A) but not in the hsp60 message. 2008/C135.25 cells
constitutively overexpressed hsp60 mRNA by 1.7 +/- 0.16 orders of magn
itude and contained a 3.8 +/- 0.45-fold higher level of HSP60 as detec
ted by immunocytochemical staining. 2008/C135.25 cells showed 1.2-fol
d cross-resistance to thermal killing. Expression of hsp60 was markedl
y reduced in 2008 xenografts as compared with 2008 cells growing in vi
tro; however, neither serum starvation nor refeeding altered the messa
ge 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 sulfox
imine, ouabain, and forskolin, did not alter hsp60 expression. These r
esults suggest a role for HSP60 in mediating resistance to both DDP an
d hyperthermia but indicate that the hsp60 mRNA levels are not regulat
ed by the factors listed above.