1998 Fiscal Year Final Research Report Summary
Molecular biologic study of telomerase activity on carcinogenesis of uterine and ovarian cancer
| Project/Area Number |
08671898
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NAGAI Nobutaka Hiroshima University Faculty of Medicine, Associate Professor, 医学部, 助教授 (90198292)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Junko Hiroshima University Faculty of Medicine, Research Associate, 医学部, 助手 (80294560)
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| Project Period (FY) |
1996 – 1998
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| Keywords | utcrinc cancer / ovarian cancer / telomerase / TRAP assay / reverse transcriptase inhibitor / semiquantitation / hTERT / hTERC antisense |
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| Research Abstract |
1. Telomerase activity in gynecologic malignancies using the TRAP assay was detected 91.7% (22/24) uterine cervical cancers, 85.2% (23/27) uterine tumors and 90.9% (30/33) ovarian cancers, respectively. In the cervical precancerous lesion, the telomerase positive rate increased along with grade of CIN.In ovary, weak telomerase activity was detected in the cortex of normal premenopausal ovary and mature cystic teratoma in benign tumor.
2. TRAP assay is also sensitive method of telomerase in cytogical materials which contained cervical cytology specimen, cavity fluid and peritoneal washings in uterine and ovarian cancer.
3. The relative telornerase activity (RTA) was calculated as the semiquantitation of telomerase activity using a DNA image analysis system (BioMax 1D), and RTA showed significantly higher in invasive cancer than precancerous lesion and benign ovarian tumor.
4. The expresion of human telomerase reverse transcriptase (hTERT) which is catalytic subunit of telomerase significantly correlated with telomerase activity (gamma=0.48, p<0.O5) and we suggest that hTERT regulate the telomerase activity.
5. In order to inhibit the transcriptase function of telomerase, the reverse transcriptase inhibitor (RTI), AZT, ddT and AZT-T, was added in the medium with human MCAS ovarian cancer cell tine and HEC-1 uterine endometrial cancer cell line. In HEC-1 cells, ddT and AZT-TP caused a decrease in telomerase activity and cell proliferation in relation to passage number and the time between passages increased. MCAS and HEC.-1 cell line which antisense hTERT was transfected by the lipofection method was also decreased telomerase activity and cell proliferation.
From these results, we suggested that semiquantitative analysis of telomerase and the detection of hThRT is the useful method for the cancer diagnosis and RTI, hTERT antisense is the effective tools for the treatment of malignancies.
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