The analysis of p53 tumor suppressor gene in human skin carcinogenesis by p53 yeast functional assay.

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The aim of this research project is to analyze the gene mutation of p53 tumor suppressor gene in various types of skin tumors by p53 yeast functional assay. We analyzed 50 cases of skin tumors and found that 2 of 10 malignant melanomas, 3 of 12 basal cell carcinomas, 3 of 5 squamous cell carcinomas, one of one eccrine gland carcinoma, 3 of 3 hair follicle carcinoma and 2 of 5 Bowen's disease had p53 mutation, One Paget's disease, one actinic keratosis, one dermatofibroma and 11 nevus cell nevi were negative for this assay. Some of positive cases with this assay were confirmed for the presence of gene mutation by DNA sequencing. Of these 50 cases, 35 cases were immunohistochemically stained with antibody against p53 protein to reveal the gene mutation and protein overexpression. Of 8 samples with overexpression of p53 protein, 6 were positive for p53 yeast functional assay. Of 27 samples without overexpression of p53 protein, only one was positive for this assay. In summary, this technique was shown to be relatively simple and sensitive for detecting p53 gene mutation. We will examine more cases of skin tumors to reveal the role of p53 gene in skin carcinogenesis by this technique in future. In addition to this research, we also have examined the role of PTCH gene in skin cancer, the correlation of telomerase activity and the expression of its subunits, the molecular mechanism of UV-induced apoptosis, the role of oxygen radical for the formation of DNA damage by UV and the epidemiology of skin cancer in Japan.