1997 Fiscal Year Final Research Report Summary
The relation of the anti-cancer drug resistance and heat shock protein 60 expression
| Project/Area Number |
07671826
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
KIMURA Eizo Jikei University school of Medicine, Department Obstetrics and Gynecology, Instructor, 医学部, 講師 (70161552)
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| Project Period (FY) |
1995 – 1997
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| Keywords | heat shock / hyperthermia / cancer / drug resistance / survival / anti-cancer drug |
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| Research Abstract |
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.
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