Regulation of HSP60 mRNA expression in a human ovarian carcinoma cell line

Cancer Chemother Pharmacol. 1993;32(4):279-85. doi: 10.1007/BF00686173.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cadmium / pharmacology
  • Chaperonin 60
  • Cisplatin / pharmacology*
  • Drug Resistance
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Growth Substances / pharmacology
  • Heat-Shock Proteins / biosynthesis
  • Heat-Shock Proteins / genetics*
  • Hot Temperature
  • Humans
  • Metallothionein / metabolism
  • Neoplasm Transplantation
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Tumor Cells, Cultured
  • Zinc / pharmacology


  • Chaperonin 60
  • Growth Substances
  • Heat-Shock Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Cadmium
  • Metallothionein
  • Zinc
  • Cisplatin