1999 Fiscal Year Final Research Report Summary
Telomerase activity and p53-induced apoptosis
| Project/Area Number |
09671682
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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 | Tottori University |
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Principal Investigator |
KIGAWA Junzo Tottori Univ. Sch. of Med., Obstetrics and Gynecology, Associated Professor, 医学部, 助教授 (00177784)
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| Co-Investigator(Kenkyū-buntansha) |
TERAKAWA Naoki Tottori Univ. Sch. of Med., Obstetrics and Gynecology, Professor, 医学部, 教授 (90163906)
KANAMORI Yasunobu Tottori Univ. Sch. of Med., Obstetrics and Gynecology, Assistant, 医学部, 助手 (70283984)
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| Project Period (FY) |
1997 – 1999
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| Keywords | telomerae / ovarian cancer apoptosis / p53 / gene-therapy / telomere |
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| Research Abstract |
Although p53 gene mutation is frequently seen in ovarian cancer, the function of p53 gene in chemosensitivity is not conclusively defined. First, we examined the relationship between chemotherapy-induced apoptosis through p53 pathway and chemosensitivity in ovarian cancer. The study suggests that p53-dependent apoptosis in tumors is strongly related to the sensitivity to chemotherapy in epithelial ovarian cancer. Next, we developed a new recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and examined the combination effect of p53 gene transfer and cis-diamminedichloroplatinum (II)(CDDP) in an ovarian cancer cell line, SK-OV-3, with deletion of the p53 gene. AxCAp53 showed a relatively high efficiency of gene transduction, and increased sensitivity to CDDP in the SK-OV-3 cells. It was found that the sensitivity of the cells to CDDP correlated to the infectious units of virus per cell of AxCAp53 in which p53 may be a potential strategy for the therapy of CDDP resistant ovarian cancer.
To elucidate the relationship between telomerase activity and chemosensitivity in epithelial ovarian cancer, telomerase activity and telomere length were investigated before and after chemotherapy. And then we found that telomerase activity may relate to chemosensitivity in epithelial ovarian cancer. While, telomerase activity may be associated with development and extension of epithelial ovarian cancer, but there is not relationship between p53 gene status and telomerase activity. Furthermore, we examined whether and how the activity of telomerase contributes p53-induced apoptosis in ovarian cancer cells. It is concluded that telomerase does not contribute p53- induced apoptosis. Therefore telomerase may be a new target for gene-therapy.
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