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

通过p53酵母功能分析分析p53抑癌基因在人类皮肤癌发生中的作用。

基本信息

批准号：
10670789
负责人：
UEDA Masato
金额：
$ 1.73万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670789/
关键词：
skin carcinogenesis p53 tumor suppressor gene yeast functional assay p53 癌抑制遺伝子

项目摘要

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.

本研究项目的目的是通过p53酵母功能分析来分析各类皮肤肿瘤中p53抑癌基因的基因突变情况。我们分析了50例皮肤肿瘤，发现10例恶性黑色素瘤中2例、12例基底细胞癌中3例、5例鳞状细胞癌中3例、1例小汗腺癌中1例、3例毛囊癌中3例、5例鲍文病中2例有p53突变、1例佩吉特病、1例光化性角化病、1例皮肤纤维瘤和11个痣细胞该检测结果痣呈阴性。通过DNA测序，该检测的一些阳性病例被证实存在基因突变。在这50例中，35例用p53蛋白抗体进行免疫组化染色，以揭示基因突变和蛋白过度表达。在 8 个 p53 蛋白过度表达的样品中，6 个 p53 酵母功能检测呈阳性。在 27 个没有 p53 蛋白过度表达的样本中，只有一个在该检测中呈阳性。总之，该技术对于检测p53基因突变相对简单且灵敏。未来我们将通过该技术检查更多的皮肤肿瘤病例，以揭示p53基因在皮肤癌发生中的作用。除此之外，我们还研究了PTCH基因在皮肤癌中的作用、端粒酶活性与其亚基表达的相关性、紫外线诱导细胞凋亡的分子机制、氧自由基在紫外线DNA损伤形成中的作用以及日本皮肤癌的流行病学。