GENES INVOLVED IN PRENEOPLASTIC PROGRESSION

这项研究的目的是识别和表征两类 参与多阶段致癌的基因。第一类是基因 具体说明对肿瘤促进剂诱导的肿瘤转化的敏感性。 第二类是指定肿瘤细胞表型表达的基因。 小鼠促进敏感性(P+)基因pro1，先前从小鼠克隆 表皮JB6细胞和测序，显示编码聚合酶的证据 核糖核酸酶保护和聚合酶证实的III-催化转录本 链式反应(PCR)分析为130聚体和175聚体。 一株新的PRO-1基因转录缺陷突变株 正在对定点突变程序进行生物检测 活动。聚合酶链式反应分析已鉴定出对推广不敏感的(P-) PRO-1的同源性及其序列正在与PRO-1的序列进行比较 分离的P+活性NO.1.活性和非活性的人ProI同源物 从鼻咽癌(NPC)细胞库中提取的 在序列水平上，目的是识别激活的突变。 鼻咽癌的几个来源，包括EB病毒(EBV)阳性和 EBV阴性的鼻咽癌已经被分析并发现有两个DNA相关 小鼠JB6受体中可检测到的活动：(1)促进转移 敏感性(P+活性)和(2)致癌转化转移(TX 活动)。一种与ras家族或某些基因无关的新的转化基因 通过人ALU筛选，从鼻咽癌细胞中克隆了另外20个癌基因 构建了鼻咽癌/JB6转基因DNA文库。鼻咽癌组织中有1.7kb的mRNA量 细胞，但在小鼠受体细胞中不存在。还检测到TX活动 结肠癌DNA，正在使用小鼠JB6受体进行鉴定 细胞。单独或成对检测到的克隆癌基因集不同于 在NIH 3T3细胞中发现了这一点。随着新的鼻咽癌基因的克隆 现在有可能研究参与基因之间的合作 致癌作用与肿瘤细胞表达相关基因 表型。关于“诱导基因”导致脑细胞活化的假说 表达“基因”将被测试。

The aim of this research is to identify and characterize two classes of genes involved in multistage carcinogenesis. The first class are genes that specify susceptibility to tumor promoter-induced neoplastic transformation. The second class are genes that specify expression of tumor cell phenotype. Mouse promotion sensitivity (P+) gene pro 1, previously cloned from mouse epidermal JB6 cells and sequenced, shows evidence for encoding polymerase III-catalyzed transcripts demonstrated by RNase protection and polymerase chain reaction (PCR) analysis to be a 130-mer and a 175-mer. Transcriptionally defective mutants of pro 1 produced by a novel site-directed mutagenesis procedure are being assayed for biological activity. PCR analysis has identified the promotion-insensitive (P-) homolog of pro 1 and the sequence of this is being compared with that of the P+ active no 1. Active and inactive human homologs of pro I isolated from a library of nasopharyngeal carcinoma (NPC) cells are being compared at the sequence level, with the aim of identifying activating mutations. Several sources of NPC, both Epstein-Barr virus (EBV)-positive and EBV-negative NPC'S, have been analyzed and found to show two DNA associated activities detectable in mouse JB6 recipients: (1) transfer of promotion sensitivity (P+ activity) and (2) transfer of oncogenic transformation (Tx activity). A novel transforming gene unrelated to the ras family or to some 20 other oncogenes has been cloned from NPC cells by human Alu screening of an NPC/JB6 transfectant DNA library. An mRNA of 1.7 kb is observed in NPC cells but not in mouse recipient cells. A Tx activity is also detected in colon carcinoma DNA and is being characterized using mouse JB6 recipient cells. The set of cloned oncogenes detected singly or in pairs differs from that found with NIH 3T3 cells. With the cloning of the new NPC oncogene it now becomes possible to study the cooperation between genes involved in induction of cancer and genes involved in expression of tumor cell phenotype. The hypothesis that "induction genes" cause activation of "expression "genes" will be tested.