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 被称为微细胞介导的染色体转移的技术， 分子癌变实验室，与Mitsuo博士合作 Oshimura(日本鸟取大学)绘制了肿瘤抑制基因图谱 人类和啮齿类动物1号染色体癌相关基因 (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)和染色体 宫颈癌、肾母细胞瘤、横纹肌肉瘤、肺癌 纤维肉瘤)。为肺定位肿瘤抑制基因 腺癌，我们已经引进了各种正常的人类染色体 微细胞介导的染色体转移入A549肿瘤细胞系 以测试哪些染色体具有抑制致瘤性的能力。 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。以前的研究 利用高转移与非转移的体细胞杂交 大鼠前列腺癌细胞证明，产生的杂交细胞是 如果保留了所有亲代染色体，则为非转移性。 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 存在表达抑制转移能力的基因(S) 前列腺癌细胞。确定同源基因的位置(S) 在人类中，特定的人类染色体被引入高度 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 不抑制体内生长速度或致瘤性的能力 杂交细胞的。人类部分基因的自发删除 在一些克隆中的11号染色体描绘了 人11号染色体对前列腺癌的抑制作用 转移瘤。这种转移抑制基因的一个候选基因是 与世隔绝。

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 non-metastatic rat prostatic cancer cells demonstrated that the resultant hybrids were non-metastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent non-random 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. A candidate gene for this metastasis suppressor was isolated.