NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS BY ONCOGENES

ras、raf、jun、erbB-2（neu）五个活化原癌基因家族 和myc与人支气管癌有关。 体外培养的人支气管上皮细胞正被用于研究 这些特定癌基因的功能作用和生长调节 致癌和肿瘤进展的基因。 erbB-2过表达 导致人支气管上皮细胞的肿瘤转化。 一个 erbB-2与转化生长之间的自分泌生长因子环 α因子可能是导致这种肿瘤的机制， 转型 对皇家空军的进一步调查显示， 激酶是其主要底物之一，并且可能是其下游效应物， raf的信号转导途径。 由于支气管肺癌的主要原因是吸烟， 最近的研究表明，烟草特有的N- 亚硝胺或香烟烟雾冷凝物引起肿瘤转化 人支气管上皮细胞。 一种自分泌循环， 可能与转化生长因子α和EGF受体有关。 这 烟草致癌作用的新的体内/体外模型应该导致新的 机械的见解和干预的机会， 化学预防

Five families of activated protooncogenes, ras, raf, jun, erbB-2 (neu) and myc have so far been associated with human bronchogenic carcinoma. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumor progression. Overexpression of erbB-2 causes neoplastic transformation of human bronchial epithelial cells. An autocrine growth factor loop between erbB-2 and transforming growth factor alpha may be the mechanism responsible for this neoplastic transformation. Further investigations of raf have revealed that PI-4 kinase is one of its major substrates and may be a downstream effector in the signal transduction pathway of raf. Since the major cause of bronchogenic carcinoma is tobacco smoke, continuing investigations have recently shown that a tobacco-specific N- nitrosamine or cigarette smoke condensate cause neoplastic transformation of human bronchial epithelial cells. An autocrine loop between transforming growth factor alpha and EGF receptor may be involved. This new in vivo/in vitro model of tobacco carcinogenesis should lead to new mechanistic insights and opportunities for intervention and chemoprevention.