| Project/Area Number |
08671876
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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 | Kanazawa University |
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Principal Investigator |
KYO Satoru University Hospital, Kanazawa University Assistant Professor, 医学部・附属病院, 助手 (50272969)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaki School of Medicine, Professor, 医学部, 教授 (10127186)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | HPV / Cervical cancer / Cell differentiation / Transcription factor / 転写調節 / AP1 / YY1 / ヒトパピローマウイルス / 癌遺伝子 |
|---|
| Research Abstract |
To clarify the molecular mechanisms through which human papillomavirus E6/E7 expression is activated during the process of cellular differentiation in stratified epithelial cells of uterine cervix, we identified core enhancer of upstream regulatory region of HPV3 1 b E6/E7 genes using transient expression assays. DNA foot print analyses and gel shift analyses identified sevral nuclear factors which bind core enhancer and regulate transcription of E6/E7 genes. In particular, Ap1 was found to be the most potent transactivator. In situ hybridization analyses revealed that E6/E7 mRNA was expressed mainly in the undifferentiated basal layers of stratified epithelial cells in uterine cervix, which was co-localized with AP1 expression determined by immunohistochemical analyses. These findings suggest that AP1 is the critical determinant of HPV oncogene expression. In addition, we found that cellular factor YY1 cooperates with API to achieve full activation of HPV oncogene expression. These results may provide insight into molecular targets for gene therapies against cervical cancer induced by HPV infection.
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