Investigation on protooncogenes in gynecologic malignancies
| Project/Area Number |
62570763
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | 佐賀医科大学 |
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Principal Investigator |
IWASAKA Tsuyoshi Saga Medical School Department of Obstetrics and Gynecology Assistant Professor, 医学部, 講師 (60117067)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yoshinobu Saga Medical School Department of Obstetrics and Gynecology Senior Lecturer, 医学部, 助手 (90156464)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Cervical carcinoma / HPV type 16 / HPV type 18 / Overexpression of oncogenes / c-myc / Ha-ras / hit and run / Amplification of oncogenes / HPV 16型 / HPV 18型 / CIN / erb B / 内因性癌遺伝子 / p21 / EGFR / 子宮頚部腺癌 / 癌遺伝子 現 / erbB / P21 / "hit and run"理論 / ヒトパピローマウイルス16型 / ヒトパピローマウイルス18型 / 2型単純ヘルペスウイルス |
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| Research Abstract |
Oncogenic potential of human papillomavirus (HPV) which is associated with occurrence of cervical carcinoma and mechanism of oncogenesis by this virus was investigated by transformation experiments in vitro. The results were obtained as follows. 1) Complete carcinogenesis can be mediated by HPV-16 or HPV-18 DNA under collaboration with other cofactors such as HSV-2.2) It is suggested that neoplastic transformation induced by HPV-18 DNA is based on "hit and run" oncogenesis. 3) HPV-16 or HPV-18 DNA can immortalize primary diploid cells and convert them to fully tumorigenic phenotype by repeating cell passage. 4) It has been experimentally proved that the difference in transforming potential exists between HPV 6/11 and HPV 16/18.5) Amplification and overexpression of c-myc oncogene was detected in transformed cells obtained by HPV-16 transfection. While overexpression of c-myc was detected in transformed cells induced by HPV-18 DNA, but no amplification was observed.
On the other hand, de
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tection of HPV DNA and amplification or overexpression of protooncogenes was performed in cervical intraepithelial neoplasias (CIN) and invasive cervical carcinomas. The results were summarized as follows. 1) HPV DNA was detected in approximately 70% of a population with CIN by in situ hybridization. CIN II showed the highest incidence of positive HPV DNA(91%),and the positive ratio decreased in CIN III(56%). 2) Immunohistochemical study of paraffin-embedded specimens with monoclonal antibodies to oncogene products revealed that only some of cervical invasive carcinomas expressed c-myc protein, ras p21 or EGFR. 3) HPV DNA was detected in 46% of invasive cervical carcinomas by Southern blot hybridization. The percentage of patients with positive results for HPV 16/18 was 29%. However, it increased up to 58% by use of polymerase chain reaction(PCR), suggesting that there are many cervical cancer tissues in which a number of cells lack viral DNA. 4) Northern blot hybridization analysis revealed overexpression of c-myc mRNA in 30% of cervical invasive carcinomas although amplification of c-myc oncogene was detected in only one of invasive carcinomas. Less
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Report
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Research Products
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