| Project/Area Number |
18591902
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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 |
Otorhinolaryngology
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| Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
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Principal Investigator |
TOKUMARU Yutaka 独立行政法人国立病院機構(東京医療センター臨床研究センター), National Hospital Organization, Tokyo Medical Center, Researcher (60245579)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Masato National Hospital Organization, Tokyo Medical Center, 東京医療センター(臨床研究センター)聴覚平衡覚研究部, Director (70129633)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,660,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | head and neck cancer / methylation / tumor suppressor gene / epigenetic / otolaryngology / 癌抑制遣伝子 |
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| Research Abstract |
DNA promoter hypermethylation is a common feature of human cancers. Moreover, genes showing cancer-specific methylation generally demonstrate tumor suppressive activity. Using our approach based on pharmacological unmasking and microarray hybridization, we identified several reactivated genes including PGP9.5. We confirmed cancer-specific PGP9.5 hypermethylation in 60% of primary head and neck squamous cell carcinomas(HNSCC).
We examined forced expression of the stable transfection of PGP9.5 in 4 HNSCC cell lines. Although all 4 cell lines demonstrated reduced log growth rates in culture after transfection, only 2 cell lines with wild type p53 demonstrated decreased growth in soft agar. In 2 cell lines with mutant p53, we observed no altered growth in soft agar and increased sensitivity to UV irradiation. These findings suggest that PGP9.5 methylation may predict invasion and the presence of a more malignant clone with poor prognosis in HNSCC. Our work supports the notion that PGP9.5 is a tumor suppressor gene inactivated by promoter methylation.
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