PERSISTENT INDUCTION OF C-FOS AND C-JUN EXPRESSION BY ASBESTOS
PERSISTENT INDUCTION OF C-FOS AND C-JUN EXPRESSION BY ASBESTOS
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DOI：
10.1073/pnas.90.8.3299
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
MOSSMAN, BT
中科院分区：
文献类型：
--
作者：
HEINTZ, NH;JANSSEN, YM;MOSSMAN, BT
为了研究石棉诱发癌变的机制，在暴露于青石棉或温石棉后，检测了大鼠胸膜间皮细胞和仓鼠气管上皮细胞中c-fos和c-jun原癌基因的表达。佛波醇 12-肉豆蔻酸酯 13-乙酸酯可诱导 c-fos 和 c-jun mRNA 快速且短暂地增加，而石棉则可导致 c-fos 和 c-jun mRNA 增加 2 至 5 倍，并在间皮细胞中持续至少 24 小时。石棉在间皮细胞中诱导 c-fos 和 c-jun mRNA 具有剂量依赖性，并且对于青石棉最为明显，青石棉是引起胸膜间皮瘤的致病性最强的石棉类型。石棉诱导 c-jun 基因表达发生在气管上皮细胞中，但不伴随相应的 c-fos 基因表达诱导。在这两种细胞类型中，石棉都会诱导蛋白质因子的增加，这些蛋白质因子特异性结合到通过 AP-1 转录因子家族介导基因表达的 DNA 位点。石棉对 AP-1 转录因子的持续诱导表明石棉诱发的致癌模型涉及通过激活包括 c-jun 和/或 c-fos 在内的早期反应基因途径来慢性刺激细胞增殖。
To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos.