GENES INVOLVED IN PRENEOPLASTIC PROGRESSION

这项研究的目的是确定和表征基因参与 细胞从正常到肿瘤表型的进展， 老鼠和人类 有证据表明这些基因参与了 动物和人类的系统都来自于观察， 肿瘤促进的不可逆转的步骤，并且动物可以被培育成 对肿瘤促进的敏感性 基因指定敏感性， 肿瘤促进剂促进小鼠肿瘤转化 表皮JB 6细胞已被克隆。 两个这样的基因，称为pro-1和 Pro-2已被识别。 他们彼此不同，彼此熟悉。 致癌基因 Pro-1已测序。 该序列是无内含子的，显示 转录和翻译所需的共有序列， 预期编码7000道尔顿的蛋白质。 肿瘤促进剂治疗 促进敏感（P+）细胞产生pro-1 RNA的瞬时增加 程度. 中国人鼻咽癌细胞（CNE）DNA显示， P+活性（通过转染）和pro-1和pro-2的同系物（通过Southern杂交） 印迹法）。 已从CNE文库中克隆了Pro-1同源物， 测定表明它们对P+活性具有生物活性。 在 此外，在P+受体细胞中可检测到一种新的转化活性， 在12-0-tetradecanoylphorbol-13-acetate（TPA）的DNA中发现了 转化的JB 6细胞。 在未来，这些研究将关注 了解原基因表达和原基因产物及其 在人类和啮齿动物细胞中的重要性。 pro基因的调控 将研究肿瘤启动子和反启动子的转录。 的 人原基因同源物结构和生物活性将被 表征了 Pro-1蛋白将被纯化、表征并 本地化。 将克隆一个新的转化基因，并对其转化模式进行研究。 将研究前基因的调节。

The aim of this research is to identify and characterize genes involved in the progression of cells from the normal to the neoplastic phenotype in mice and humans. Evidence suggesting the involvement of such genes in animal and human systems has come from the observations that there are irreversible steps in tumor promotion and that animals can be bred for sensitivity to tumor promotion. Genes that specify sensitivity to promotion of neoplastic transformation by tumor promoters in mouse epidermal JB6 cells have been cloned. Two such genes, termed pro-1 and pro-2, have been identified. These differ from each other and from known oncogenes. Pro-1 has been sequenced. The sequence is intronless, shows the consensus sequences needed for transcription and translation and is expected to code for a 7000 dalton protein. Tumor promoter treatment of promotion sensitive (P+) cells produces transient increases in pro-1 RNA levels. Chinese human nasopharyngeal carcinoma cell (CNE) DNA shows both P+ activity (by transfection) and homologs of pro-1 and pro-2 (by Southern blotting). Pro-1 homologs have been cloned from a CNE library and initial assays indicate that they are biologically active for P+ activity. In addition, a novel transforming activity detectable in P+ recipient cells has been found in the DNA of 12-0-tetradecanoylphorbol-13-acetate (TPA) transformed JB6 cells. In the future, these studies will be concerned with understanding pro gene expression and pro gene products and their significance in human and rodent cells. The regulation of pro gene transcription by tumor promoters and antipromoters will be studied. The structure and biological activity of human pro gene homologs will be characterized. Pro-1 proteins will be purified, characterized and localized. A novel transforming gene will be cloned and its mode of regulation by pro genes will be studied.