Bernstein L R, Colburn N H
Johns Hopkins University, Department of Biology, Baltimore, MD 21218.
Science. 1989 May 5;244(4904):566-9. doi: 10.1126/science.2541502.
Tumor promoters may bring about events that lead to neoplastic transformation by inducing specific promotion-relevant effector genes. Functional activation of the transacting transcription factor AP-1 by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) may play an essential role in this process. Clonal genetic variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to promotion of transformation by TPA were transfected with 3XTRE-CAT, a construct that has AP-1 cis-enhancer sequences attached to a reporter gene encoding chloramphenicol acetyltransferase (CAT). Transfected JB6 P+, but not P- variants, showed TPA-inducible CAT synthesis. Epidermal growth factor, another transformation promoter in JB6 cells, also caused P+ specific induction of CAT gene expression. These results demonstrate an association between induced AP-1 function and sensitivity to promotion of neoplastic transformation.
肿瘤促进剂可能通过诱导特定的促进相关效应基因引发导致肿瘤转化的事件。佛波酯12-O-十四酰佛波醇-13-乙酸酯（TPA）对反式作用转录因子AP-1的功能激活可能在此过程中起关键作用。用3XTRE-CAT转染对TPA诱导转化敏感（P+）或抗性（P-）的小鼠表皮JB6细胞的克隆遗传变体，该构建体具有与编码氯霉素乙酰转移酶（CAT）的报告基因相连的AP-1顺式增强子序列。转染的JB6 P+变体而非P-变体显示出TPA诱导的CAT合成。表皮生长因子是JB6细胞中的另一种转化促进剂，也导致了CAT基因表达的P+特异性诱导。这些结果证明了诱导的AP-1功能与对肿瘤转化促进的敏感性之间的关联。
