GENES INVOLVED IN PRENEOPLASTIC PROGRESSION

这项研究的目的是识别和表征特定的基因 小鼠对肿瘤启动子诱导的肿瘤转化的敏感性 和人类。有证据表明这些基因参与了动物 人类系统是从观察到动物可以繁殖出来的 对肿瘤促进的敏感性。两个基因指定了对 肿瘤促进剂对小鼠肿瘤转化的促进作用 表皮JB6细胞此前已被克隆。这些假定的基因， 命名为PRO-1和PRO-2的基因已经测序，并正在进行特征分析 关于激活的方式和表达的调节。基因组学 中国人鼻咽癌细胞系CNE2的DNA 对耐药小鼠细胞的促进敏感性(P+)活性。这 活性至少部分归因于小鼠激活的同系物 PRO-1，用小鼠PRO-1筛选CNE2基因组文库 转染腺病毒同源基因后P+活性的检测 耐药小鼠细胞。从正常人中分离的非活性Pro-1同源物 将人类文库和CNE2文库与激活的文库进行比较 CNE2PRO-1，以确定激活模式。两个cDNA文库，一个 来自启蒙促进诱发的皮肤乳头状瘤，另一个来自 鳞癌，每个都产生了与Pro-2同源的克隆 包含一个2.1kb的cDNA.这一发现具有重要意义，因为它不仅 促进基因组克隆中内含子-外显子的分配，但也打开了 PRO-2表达在体内癌变中的作用研究

The aim of this research is to identify and characterize genes that specify susceptibility to tumor promoter-induced neoplastic transformation in mice and humans. Evidence suggesting the involvement of such genes in animal and human systems has come from the observation that animals can be bred for sensitivity to tumor promotion. Two genes that specify sensitivity to promotion of neoplastic transformation by tumor promoters in mouse epidermal JB6 cells have been previously cloned. These putative genes, termed pro-1 and pro-2, have been sequenced and are being characterized with respect to mode of activation and regulation of expression. Genomic DNA of a Chinese nasopharyngeal carcinoma cell line, CNE2, confers promotion sensitivity (P+) activity on resistant mouse cells. This activity is, at least in part, attributable to activated homologs of mouse pro-1, as shown by screening a CNE2 genomic library with a mouse pro-1 probe and testing the homologs for P+ activity after transfection into resistant mouse cells. Inactive pro-1 homologs isolated from a normal human library and from the CNE2 library are being compared with activated CNE2 pro-1 to ascertain the mode of activation. Two cDNA libraries, one from initiation-promotion induced skin papillomas and the other from a squamous carcinoma, have yielded clones homologous to pro-2, each containing a 2.1 kb cDNA. This finding is significant in that it not only facilitates intron-exon assignment in the genomic clone but also opens up investigation of the role of pro-2 expression in carcinogenesis in vivo.