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.

有越来越多的证据表明存在肿瘤家族 与不同癌症有关的抑制基因。 使用技术 被称为微球介导的染色体转移，实验室 分子癌变与Mitsuo Oshimura博士合作 （日本托托里大学）已绘制了参与的肿瘤抑制基因 人类和啮齿动物癌为1染色体（子宫内膜癌， 纤维肉瘤），3染色体（肾癌，肺癌），染色体6 （子宫内膜癌），7号染色体（绒毛膜瘤），染色体9 （子宫内膜癌）和11号染色体（宫颈癌，威尔姆斯的肿瘤， 横纹肌肉瘤，肺癌，纤维肉瘤）。 绘制抑制肿瘤 肺腺癌的基因，我们引入了各种正常人 微球介导的染色体进入A549肿瘤细胞系的染色体 转移以测试哪种染色体有能力抑制 肿瘤性。 这些结果表明3和11染色体可以 抑制A549肺腺癌细胞的致瘤性。 以前的 使用高度转移和的体细胞杂交研究 非转移大鼠前列腺癌细胞表明该结果 如果所有父母染色体都是 保留。 体细胞杂种隔离剂，未经随机染色体 损失重新表达了高转移能力。 这些结果证明了这些结果 有一些基因的表达可以抑制转移性能力 前列腺癌细胞。 确定同源基因在 将人类特定的人类染色体引入了高度 使用Microcell介导的转移大鼠前列腺癌细胞 染色体转移。 将人类染色体11引入高度 转移性大鼠前列腺癌细胞导致转移性抑制 不抑制体内生长速率或肿瘤性的能力 杂种细胞。 人类染色体的部分自发删除11 在某些克隆中，描绘了人类染色体11的最小部分 能够抑制前列腺癌转移作为区域 11P11.2-13，但不包括Wilms的肿瘤1基因座。