ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENES IN CHEMICAL CARCINOGENESIS

越来越多的证据表明存在一种肿瘤家族 参与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，该实验室 分子癌变，与大村三夫博士合作 (日本鸟取大学)，已经绘制了涉及 人类和啮齿动物癌症到1号染色体(子宫内膜癌， 纤维肉瘤)，染色体3(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)。绘制肿瘤抑制基因图谱 肺腺癌的基因，我们已经介绍了各种正常人 微细胞介导的染色体导入A549肿瘤细胞系的研究 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。上一首 高转移性和高转移性肺癌的体细胞杂交研究 非转移性大鼠前列腺癌细胞证明 如果所有的亲本染色体都是 保留。经历非随机染色体的体细胞杂种分离体 损失重新体现了高转移能力。这些结果证明了 有基因(S)的表达可以抑制肺癌的转移能力 前列腺癌细胞。同源基因(S)的定位研究 人类，特定的人类染色体被引入到高度 微细胞介导的转移性大鼠前列腺癌细胞 染色体转移。人11号染色体导入HIGHERY 转移的大鼠前列腺癌细胞导致转移抑制 能够在不抑制体内生长速度或致瘤性的情况下 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的区域 11p11.2-13，但不包括Wilms‘Tumor-1基因。

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.