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

p53 家族新成员 - p73、p51 和 p40 在脑肿瘤中的功能作用研究

• 批准号: 11470282
• 负责人: TADA Mitsuhiro
• 金额: $ 9.22万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470282/
• 关键词: p53 family; p73; p51; p63; p40; brain tumor

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.

在这项研究中，我们研究了新的p53家族成员p73、p51和p40在人脑肿瘤中的功能作用。我们开发了新的基于酵母的分析方法来测量p73和p63的转录活性，并将其应用于脑瘤。1)对52例胶质母细胞瘤和脑膜瘤进行了酵母p73功能检测，未发现p73基因突变。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.，2001)2.已知隐性p53突变体可以特异性地抑制p73。我们发现了Arg72的等位基因特异性选择，它通过隐性的p53突变来强烈抑制p73，而不是通过显性的负p53突变(Carcinenetic，2001)。3)我们报道了在人类肿瘤中发现的p73突变-P405R和P425L的转录活性(Oncogene，2001)。4)我们建立了p53、p73和p63肿瘤抑制基因的定量转录分析，并将很快发表结果。

项目成果

Nozaki M: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression"Neuro-oncology. 1. 149-162 (1999)

Nozaki M：“p53 和其他基因功能丧失在星形细胞瘤肿瘤发生和进展中的作用”神经肿瘤学。

Tada M, Furuuchi K, et al.: "Inactivate the Remaining p53 Allele or the Alternate p73? -Preferential selection of the Arg 72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants."Carcinogenesis. (in press). (2001)

Tada M、Furuuchi K 等人：“使剩余 p53 等位基因或替代 p73 失活？ - 在具有隐性 p53 突变体但不具有跨显性突变体的癌症中优先选择 Arg 72 多态性。”致癌作用。

Ozaki, T., Tada M., et al.: "Deletion of the C-terminal region of p73α enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Research. 59. 5902-5907 (1999)

Ozaki, T., Tada M., et al.：“p73α C 末端区域的缺失增强了其反式激活功能和 DNA 结合活性，但抑制了哺乳动物细胞凋亡的诱导”癌症研究 59. 5902-5907。 (1999)

Nozaki M: "p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade"Brain Pathol. 11. 296-305 (2001)

Nozaki M：“通过功能性酵母测定确定，p73 在脑膜瘤中没有突变，但 p73 表达随着肿瘤级别的增加而增加”Brain Pathol。

Ozaki T: "Deletion of the COOH-terminal region ofp73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Res. 59. 5902-5907 (1999)

Ozaki T：“删除 p73α 的 COOH 末端区域可增强其反式激活功能和 DNA 结合活性，但会抑制哺乳动物细胞凋亡的诱导”Cancer Res。