| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Genomic DNA was extracted from squamous cell carcinoma of the skin (n=12), malignant melanoma (n=9), and basal cell carcinoma (n=10), and subjected for methylation-specific PCR. DNA methylation in the promoter or 5'- coding region of p16, p14, p15, E-cadherin, von Hippel-Lindau genes were observed in 8 cases, 2 cases, none, 12 cases, and none of the squamous cell carcinoma, respectively, 3 cases, none, none, 4 cases, none of malignant melanoma, and 3 cases, none, none, 4 cases, none of basal cell carcinoma.
In genomic analyses of squamous cell carcinoma loss of heterozygosity or mutation of E-cadherin gene were not detected. Among E-cadherin DNA methylation-positive cases E-cadherin protein expression was abruptly diminished between the tumor and the surrounded normal tissue. The E-cadherin expression in squamous cell carcinoma was suppressed through DNA methylation.
Furthermore, squamous cell carcinoma, malignant melanoma, and basal cell carcinoma, one case each, were subjected to tissue culture, in the medium supplemented with 5'-aza-2'-deoxycytidine or trichostatin A. Extracted RNA was amplified, and hybridized onto Human 1A Oligo Microarray (Agilent). De-methylation of DNA lead the re-expression of tumor suppressor genes.
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