| Project/Area Number |
19591937
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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 | Saga University |
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Principal Investigator |
IWASAKA Tsuyoshi Saga University, 医学部, 教授 (60117067)
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| Co-Investigator(Kenkyū-buntansha) |
JOH Keiichiro 佐賀大学, 医学部, 准教授 (90124809)
NAKAO Yoshihumi 佐賀大学, 医学部, 講師 (30336119)
野口 光代 佐賀大学, 医学部, 助教 (20432958)
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| Project Period (FY) |
2007 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 婦人科腫瘍学 / 子宮頸癌 / エピジェネティクス / メチル化 / ヒストン修飾 / HPV / 子宮頸部病変 / RAR β2 / DNAメチル化 / HPV陰性子宮頸癌 / RARβ2 |
|---|
| Research Abstract |
To elucidate the silencing mechanism of retinoic acid receptor β2 (RARβ2) in cervical carcinogenesis, we investigated RARβ2 expression and the status of both DNA methylation and histone modifications at the promoter in cervical cancer celllines. RARβ2 was frequently repressed in cancer cell lines and in primary cancers ofthe cervix. Although the majority of RARβ2-negative cancers had methylated promoter, RARβ2 was repressed with hypomethylated promoter in a substantial fraction of the cancers. The RARβ2-negative cells with hypomethylated promoters showed a repressive histone modification pattern at the promoter. RARβ2 was reactivated by a histone deacetylase inhibitor, accompanied by formation of active histone modifications. The repressive modification was also observed in cells repressed with hypermethylated promoter, but RARβ2 was reactivated only by DNA demethylating agent and not by histone deacetylase inhibitor. Our results suggest that RARβ2 is silenced by either of the two key epigenetic pathways, DNA methylation or repressive histone modifications, depending on the individual cancer cells. Furthermore, DNA demethylating agent and histone deacetylase inhibitor might be useful for the treatment of cervical cancers.
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