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。第一个类包括 与肿瘤启动子诱导肿瘤易感性相关的基因 转型。第二类包括指定表达的基因 肿瘤细胞表型。小鼠JB6启动子抗性(P-)， 促进敏感(P+)和致瘤(TX)JB6来源的表皮细胞 已经发现不同的品系在几个基因的表达上存在差异 在随附的项目ZOICPO5383-08 LVC中描述，“膜信号 肿瘤促进中的转导。这些基因表达的变化 从P-到P+再到Tx表型进展过程中的基因似乎是 在这些稳定的变异细胞系中受到基因控制。我们有 最近发现对肿瘤促进剂的反应发生了稳定的变化 JB6来源的致瘤细胞系。这一变化涉及收购一家 蛋白激酶C激活剂对细胞的杀伤反应 细胞表现出以细胞凋亡为特征的DNA损伤类型 (程序性细胞死亡)。一种新的变换相关序列 已从人鼻咽部克隆出与任何已知癌基因无关的基因 人ALU筛选NPC/JB6基因转染体的研究 基因组文库。在鼻咽癌组织中观察到1.7kb的杂交mRNA 细胞，但在小鼠受体细胞中不存在。一种新分离的鼻咽癌基因 克隆人正在进行分析。此外，两个独立的鼻咽癌细胞株 在肿瘤的一个“热点”中显示相同的表达突变 抑制基因P53因此似乎将其激活为癌基因。 我们正在向我们提供来自台湾患者的更多鼻咽癌样本 用于检查与新克隆的NPC转化相关的 基因和P53基因的转化相关突变。最后，我们 已经了解到JB6 P+细胞可以通过以下方式转化为肿瘤表型 激活的v-H-ras、v-raf或src的过表达，但不是以下任何一种 其他几个致癌基因。这些细胞的基因表达谱 正在检测JB6/癌基因转基因细胞系以增加我们的 理解JB6_MODEL中的转化路径。

The aim of this research is to identify and characterize two classes of genes involved in multistage carcinogenesis. The first class includes genes associated with susceptibility to tumor promoter-induced neoplastic transformation. The second class includes genes that specify expression of tumor cell phenotype. Mouse JB6 promotion-resistant (P-), promotion-sensitive (P+), and tumorigenic (Tx) JB6-derived epidermal cell lines have been found to differ in the expression of several genes described in the accompanying project ZOICPO5383-08 LVC, "Membrane Signal Transduction in Tumor Promotion." The changes in expression of these genes during the progression from P- to P+ to Tx phenotypes appear to be genetically controlled in these stable variant cell lines. We have recently discovered a stable change in a response to tumor promoters by a JB6-derived tumorigenic cell line. The change involves acquisition of a cell-killing response to activators of protein kinase C. The treated cells show the type of DNA damage that characterizes apoptosis (programmed cell death). A novel transformation-associated sequence unrelated to any known oncogene has been cloned from human nasopharyngeal carcinoma (NPC) cells by human Alu screening of an NPC/JB6 transfectant genomic library. A hybridizing mRNA of 1.7 Kilobase is observed in NPC cells but not in mouse recipient cells. A recently isolated NPC cDNA clone is being analyzed. In addition, two independent NPC cell lines show the same expressed mutation in one of the "hot spots" of the tumor suppressor gene, p53, thus appearing to activate it to an oncogene. Additional NPC samples from Taiwanese patients are being provided to us for examination of both the newly cloned NPC transformationassociated gene and the p53 gene for transformation-relevant mutations. Finally, we have learned that JB6 P+ cells can be transformed to a tumor phenotype by overexpression of activated v-H-ras, v-raf, or src, but not by any of several other oncogenes. The profiles of gene expression in these JB6/oncogene transfectant cell lines are being examined to increase our understanding of transformation pathways in the JB6_ model.