TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR CARCINOMA

人类肝细胞癌中的抑癌基因

• 批准号: 5201547
• 负责人: E TABOR
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201547
• 关键词: Asia; United States; binding proteins; clone cells; gene expression; gene mutation; genetic polymorphism; hepatoblastoma; hepatocellular carcinoma; human genetic material tag; human tissue; hyperplasia; molecular cloning; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; single strand conformation polymorphism; transfection /expression vector; tumor suppressor genes

Studies using single-strand conformation polymorphism and sequencing have been used to identify p53 mutations in several populations. Mutations of p53 were identified in 11/35 (31%) hepatocellular carcinomas (HCCs) from Korea. Only one of these mutations was at the "hot spot" at codon 249, a mutation that has long been associated with aflatoxin as a possible etiologic factor; thus, aflatoxin appears to play very little role in the development of HCC in Korea. This is consistent with the lack of aflatoxin in the food in Korea and the prominent role of hepatitis B virus (HBV) as a cause of HCC in Korea. Similar studies conducted in this laboratory in a United States population were unusual because: 1) Although mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have not been previously reported. 2) Most studies have focused on p53 exons 4-9; all p53 exons (1 through 11) were studied here for the first time. Abnormalities of the p53 gene were found in 5/12 (42%) HCCs. No mutations of p53 were found at hot- spot codon 249; the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA. A recombinant vaccinia virus was constructed using the wild-type human p53 gene as an insert. The p53 protein produced by this recombinant virus was used to investigate p53 binding proteins in 17 cell lines, including 10 derived from HCC, four from other human cancers, and three from non-human primate tissues. In all 17 cell lines tested; two proteins of 40 kD and 50 kD were identified that bound to wild-type p53 and that may be cellular regulators of p53 function.

利用单链构象多态性和测序技术进行研究