ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS

抑癌基因和癌基因在化学致癌中的作用

• 批准号: 3841068
• 负责人: J C BARRETT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 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/3841068
• 关键词: Wilms' tumor; chemical carcinogenesis; chromosome deletion; clone cells; cytogenetics; gene expression; genetic mapping; human genetic material tag; human tissue; hybrid cells; lung neoplasms; neoplasm /cancer genetics; neoplastic cell; oncogenes; prostate neoplasms; tissue /cell culture; transfection; tumor suppressor genes

There is increasing evidence for the existence of a family of tumor suppressor genes that are involved in different cancers. Using a technique known as microcell-mediated chromosome transfer, the Laboratory of Molecular Carcinogenesis, in collaboration with Dr. Mitsuo Oshimura (Tottori University, Japan), has mapped tumor suppressor genes involved in human and rodent cancers to chromosome 1 (endometrial cancer, fibrosarcomas), chromosome 3 (renal cancer, lung cancer), chromosome 6 (endometrial cancer), chromosome 7 (choriocarcinoma), chromosome 9 (endometrial cancer), and chromosome 11 (cervical cancer, Wilms' tumor, rhabdomyosarcoma, lung cancer, fibrosarcoma). To map tumor suppressor genes for lung adenocarcinomas, we have introduced various normal human chromosomes into the A549 tumor cell line by microcell-mediated chromosome transfer to test which chromosomes had the ability to suppress tumorigenicity. These results indicate that chromosome 3 and 11 can suppress the tumorigenicity of A549 lung adenocarcinoma cells. Previous studies using somatic cell hybridization of highly metastatic and nonmetastatic rat prostatic cancer cells demonstrated that the resultant hybrids were nonmetastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent nonrandom chromosomal losses reexpressed high metastatic ability. These results demonstrated that there are gene(s) whose expression can suppress metastatic ability of prostatic cancer cells. To identify the location of homologous gene(s) in the human, specific human chromosomes were introduced into highly metastatic rat prostatic cancer cells using the microcell-mediated chromosome transfer. Introduction of human chromosome 11 into highly metastatic rat prostate cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells. Spontaneous deletion of portions of human chromosome 11 in some of the clones delineated the minimal portion of human chromosome 11 capable of suppressing prostatic cancer metastases as the region between 11p11.2-13 but not including the Wilms' tumor-1 locus.

越来越多的证据表明肿瘤家族的存在 涉及不同癌症的抑制基因。 使用一种技术 被称为微细胞介导的染色体转移，实验室 分子癌变，与 Mitsuo Oshimura 博士合作 （鸟取大学，日本）绘制了涉及肿瘤抑制基因的图谱 人类和啮齿动物 1 号染色体癌症（子宫内膜癌、 纤维肉瘤）、3 号染色体（肾癌、肺癌）、6 号染色体 （子宫内膜癌）、7 号染色体（绒毛膜癌）、9 号染色体 （子宫内膜癌）和 11 号染色体（宫颈癌、肾母细胞瘤、 横纹肌肉瘤、肺癌、纤维肉瘤）。 绘制抑癌基因图谱 肺腺癌的基因，我们引入了各种正常人 通过微细胞介导的染色体将染色体导入A549肿瘤细胞系 转移以测试哪些染色体具有抑制能力 致瘤性。 这些结果表明 3 号和 11 号染色体可以 抑制A549肺腺癌细胞的致瘤性。 以前的 使用体细胞杂交的研究高度转移和 非转移性大鼠前列腺癌细胞证明，所得 如果所有亲本染色体都是非转移性的，则杂交体是非转移性的 保留。 经过非随机染色体分离的体细胞杂种分离子 损失重新表达了高转移能力。 这些结果表明 存在其表达可以抑制肿瘤转移能力的基因 前列腺癌细胞。 确定同源基因的位置 人类，特定的人类染色体被引入高度 使用微细胞介导的转移性大鼠前列腺癌细胞 染色体转移。 将人类11号染色体引入高度 转移性大鼠前列腺癌细胞导致转移抑制 能力而不抑制体内生长速率或致瘤性 杂交细胞。 人类 11 号染色体部分自发缺失 在一些克隆中描绘了人类 11 号染色体的最小部分 能够抑制前列腺癌转移 11p11.2-13，但不包括 Wilms 肿瘤-1 基因座。