| Budget Amount *help |
¥3,740,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
In 2006, we determined DNA methyaltion profiles of p14, p16, Apc, GSTP, and cyclin D2 genes in tongue dysplasias, papillomas, and squamous cell carcinomas induced by 4-nitroquinoline 1-oxide in rasH2 mice. We observed different methylation profiles in these genes during tongue carcinogenesis. Especially the rates of hypermethylation of Apc and cyclin D2 increased during the carcinogenesis.
In 2007, we investigated the presence of mythylation in the tongue dysplastic lesions (n=50) and squamous cell carcinoma(n=24) that are positive (25 dysplasias and 12 carcinomas) or negative (25 dysplasias and 12 carcinomas) for GSTP immunohistochemistry using methylation-specific PCR. The rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 42%, 58%, 37%, 35%, 24% in the GST-P-positive dysplasia and 31%, 29%, 31%, 28%, 10% in the GSTP-negative dysplasia. Also, we observed that the rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 50%, 67%, 52%, 68%, 40% in the GST-P-positive carcinoma and 33%, 31%, 40%, 24%, 19% in the GSTP-negative carcinoma. Our findings suggest that dysplasias positive for GST-P might be direct precursor lesions for tongue malignancy and that hypermethylation in certain genes functioning cell growth and apoptosis and those related to detoxification is involved in tongue carcinogenesis.
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