Investigation of Functional Roles of New p53 Family Members - p73, p51, and p40 in Brain Tumors

在本研究项目中，我们研究了新的p53家族成员- p73，p51和p40在人类脑肿瘤中的功能作用。我们开发了新的基于酵母的检测方法来测量p73和p63的转录活性，并应用于脑肿瘤。结果表明：1）我们应用新开发的酵母p73功能检测法检测了52例胶质母细胞瘤和脑膜瘤，未发现p73突变。然而，我们发现p73的α、β、γ和ε亚型的表达与脑膜瘤的恶性程度相关（Brain Pathol.，2）已知隐性p53突变体特异性抑制p73。我们发现Arg 72的等位基因特异性选择，它强烈抑制p73，通过隐性p53突变，而不是通过显性负性p53突变（Carcinogenesis，2001）。3）我们报道了在人类肿瘤中发现的p73突变体-P405 R和P425 L的转录活性（Oncogene，2001）。4）我们开发了p53、p73和p63肿瘤抑制因子的定量转录测定，并将尽快发表结果。

In this research project, we investigated functional roles of new p53 family members - p73, p51, and p40 in human brain tumors. We developed new yeast-based assays to measure transcriptional activity of p73 and p63 and applied to brain tumors. As the results, we obtained the followings:1) We applied a newly developed yeast p73 functional assay to a total of 52 cases of glioblastoma and meningioma, and found no p73 mutation in these tumors. We showed, however, that expression of α, β, γ, and ε isoforms of p73 correlates with malignancy of meningioma (Brain Pathol., 2001).2) Recessive p53 mutants are known to specifically inhibit p73. We showed an allele specific selection of Arg72, which strongly inhibits p73, by recessive p53 mutation, but not by dominant negative p53 mutations (Carcinogenesis, 2001).3) We reported transcriptional activity of p73 mutants - P405R and P425L found in human tumors (Oncogene, 2001).4) We developed a quantitative transcriptional assay for p53, p73, and p63 tumor suppressors, and will publish the results as soon.