TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR CARCINOMA

人类肝细胞癌中的抑癌基因

• 批准号: 3774899
• 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/3774899
• 关键词: China; Europe; freeze etching; gene deletion mutation; gene expression; hepatitis B virus group; hepatoblastoma; hepatocellular carcinoma; human tissue; immunocytochemistry; liver neoplasms; mutant; northern blottings; restriction fragment length polymorphism; tumor suppressor genes; viral carcinogenesis; virus antigen; western blottings

The expression of the p53 and RB tumor suppressor genes in seven human hepatocellular carcinoma and hepatoblastoma cell lines was evaluated by northern and western blot and immunohistochemistry. The expression of p53 was abnormal as indicated by the absence of detectable p53 RNA or the overexpression of p53 protein in five of the seven cell lines; the overexpressed p53 protein appeared to be the product of a mutant p53 gene. Although RB RNA was detectable in all seven cell lines, RB protein was undetectable in three of the cell lines but was detectable in the other four. The RB tumor suppressor gene product was examined by immunohistochemistry in frozen sections from 14 human HCCs from China. Hepatitis B surface antigen (HBsAg) was detectable in adjacent nontumorous liver from all 14 HCC patients. RB protein was absent from HCC cells of 3/14 (21%) HCCs. Abnormalities of the RB gene were analyzed within exons 12-23 by single- strand conformation polymorphism (SSCP) using five overlapping segments of 129 to 337 nucleotides each. Five cell lines derived from human HCCs were studied. (All mutations or deletions of the RB gene reported in other human cancers have encompassed portions of exons 12-23. Deletions in the RB cDNA were found in exons 17-21 in two of the cell lines, and in exons 20-21 in the third cell line. The exons examined were normal in the remaining cell lines. p53 was examined by immunohistochemistry in tissues of liver tumors that are thought to be possible precursors of HCC, as well as HCCs, from Hungarian patients. Mutant p53 was detected in 8 of 16 HCCs and in none of 23 benign liver tumors.

P53和Rb抑癌基因在7例人类组织中的表达 肝细胞癌和肝母细胞瘤细胞系的评价 Northern和Western印迹和免疫组织化学。抑癌基因P53的表达 异常，表现为没有可检测到的p53 RNA或 在7个细胞系中有5个细胞系P53蛋白过表达； 过表达的P53蛋白似乎是突变型P53基因的产物。 虽然在所有七种细胞系中都能检测到Rb RNA，但Rb蛋白是 在三个细胞系中检测不到，但在另一个细胞系中可检测到 四。 用免疫组织化学方法检测Rb抑癌基因产物 取自中国的14个人肝细胞癌的冰冻切片。乙肝表面 在所有14例患者的邻近非肿瘤性肝脏中均可检测到抗原(HBs Ag) 肝细胞癌患者。3/14(21%)的肝癌细胞中Rb蛋白缺失。 对Rb基因外显子12-23进行单链构象分析。 利用5个重叠片段的链构象多态性(SSCP) 每个核苷酸为129到337个核苷酸。从人肝癌细胞来源的5个细胞系 学习。(在其他报告的Rb基因的所有突变或缺失 人类癌症包含了外显子12-23的一部分。中的删除 Rb基因在两个细胞系的外显子17-21和外显子中均有表达 20-21在第三代细胞系中。所检测的外显子在 剩下的细胞系。 用免疫组织化学方法检测肝肿瘤组织中P53蛋白的表达。 被认为是肝细胞癌和肝癌的可能前体，来自 匈牙利病人。16例肝癌中有8例检测到突变型P53，无一例检测到突变型P53 在23个良性肝脏肿瘤中。