| Project/Area Number |
05671380
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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 | Saga Medical School |
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Principal Investigator |
IWASAKA Tsuyoshi Saga Med.Sch.Associate Professor, 医学部, 助教授 (60117067)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Masatoshi Saga Med.Sch.Instructor, 医学部, 助手 (40230669)
松尾 憲人 佐賀医科大学. 医学部, 助手 (30244015)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | cervical carcinoma / human papillomavirus / co-factor / oncogene / anti-oncogene / immortalization / oncogenesis / 子宮頸癌 / ヒトパピローマ ウイルズ / 不死化細胞 |
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| Research Abstract |
(1) Four immortalized cell lines (HEN-16, HEN-18, HEC-16, and HEC-18-1) were established by transfection of HPV 16 and 18 DNA into endocervical and ectocervical cells.
(2) In vivo transplantation system revealed that immortalized cell lines derived from endocervical epithelium (HEN-16, HEN-18) formed higher grade lesion than those from ectocervical epithelium and their expression patte of cytokeratin coincided with that of adenocarcinoma of the cervix, which shows that these cell lines can be a model for a precursor lesion of cervical adenocarcinoma.
(3) In the process of HPV-18-induced immortalization, it is revealed that precrisis culture contained more than 100 copies/cell of episomal HPV-18 DNA and no detectable integrated viral NDA,while the postcrisis cells contained a low copy number of only iontegrated viral genome. The northern blot patterns of E6-E7 and E2/E4 RNA were different between the cells before and after crisis. These results suggest that, although insufficient for tumorigenic transformation, viral DNA integration during crisis is associated with the establishment of an immortalized phenotype.
(4) A tumorigenic cell line (HEC-18-1C) was established after treatment of immortalized HEC-18-1 cells with cigarette smoke condensate. Fomed tumor was invasive squamous cell carcinoma. The result suggests the role of cigarette smoke in the progression of HPV-initiated carcinogenesis of the cervix.
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