GENES INVOLVED IN PRENEOPLASTIC PROGRESSION

这项研究的目的是识别和表征 指定对肿瘤启动子诱导的肿瘤的易感性 老鼠和人类的转变。有证据表明 这些基因在动物和人类系统中的参与已经到来 从观察到动物可以被培育出来是为了对 肿瘤促进剂。决定晋升敏感性的两个基因 肿瘤促进剂对小鼠肿瘤转化的影响 表皮JB6细胞此前已被克隆。这些推定 被称为PRO-1和PRO-2的基因已经测序，并正在进行 具有激活和调节方式的特点的 表达的方式。独特的PRO-1杂交转录本已经 在小鼠细胞质和Poly(A)+RNA中鉴定。P细胞 该转录本的表达水平低于P+或细胞 由肿瘤促进剂12-0-十四酰佛波醇转化- 13-乙酸酯(TPA)，提示过度表达是一种可能的方式 激活。一例中国人鼻咽癌的基因组DNA CNE2细胞株具有促进敏感性(P+)活性 耐药小鼠细胞。这项活动至少在一定程度上， 归因于激活的小鼠PRO-1同源物，如所示 用小鼠PRO-1探针筛选CNE2基因组文库 转染腺病毒后检测同系物的P+活性 耐药小鼠细胞。从沙门氏菌中分离的非活性PRO-1同系物 正常人类文库和CNE2文库正在被 与活化的CNE2Pro-1进行比较，以确定其作用模式 激活。异源双链分析正在进行，以确定 非同源序列。嵌合构建物的分析 来自人类PRO-1的P+活性或非活性的序列是 预计将阐明对生物活性至关重要的序列。 两个cDNA文库，一个来自启动促进诱导的皮肤 乳头状瘤和另一例来自鳞癌， 获得了与Pro-2同源的克隆，包含cdna片段。 分别为2.1和0.9kb。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 对PRO-2表达在人类免疫缺陷中的作用的研究 体内致癌作用。

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. Unique pro-1-hybridizing transcripts have been identified in mouse cytoplasmic and poly(A)+ RNA. P- cells express lower levels of this transcript than do P+ or cells transformed by the tumor promoter, 12-0-tetradecanoylphorbol- 13-acetate (TPA), suggesting overexpression as a possible mode of activation. 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. Heteroduplex analysis is being carried out to pinpoint nonhomologous sequences. Assay of chimeric constructs of sequence from human pro-1 that is P+ active or inactive is expected to elucidate sequences critical to biological activity. Two cDNA libraries, one from initiation-promotion induced skin papillomas and the other from a squamous carcinoma, have yielded clones homologous to pro-2, containing cDNA fragments of 2.1 and 0.9 kb. 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.