NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS BY ONCOGENES OR CARCINOGENS

原癌基因激活的五个家族：ras、raf、jun、erbB-2和myc 到目前为止，已经发现了与人类肺癌有关的基因。人类 体外培养的支气管上皮细胞正被用来研究 这些特定癌基因和生长调控基因的功能作用 在癌症发生和肿瘤进展中起重要作用。人支气管上皮 Ha-ras癌基因已转化成肿瘤细胞。鉴于 激活的ras基因在体外的表达不是必需的。 细胞的生长，Ha-ras的表达与选择性 体内生长优势。稳态的一种逆关联 凝血酶反应蛋白mRNA和蛋白表达与肿瘤恶性进展的关系 癌基因(Ha-、k-和N-ras)转化的人支气管上皮细胞 已经被观察到了。细胞周期中G1检查点的失调 可能会导致肿瘤转化。转基因细胞的过表达 细胞周期蛋白D1基因对人食道细胞生长的促进作用 负生长因子、转化生长因子-β1。人类基因组的不稳定性 蛋白转染法诱导支气管上皮细胞分化 磷酸裂解酶基因，cdc25A或cdc25B。相比之下，基因组的不稳定性或 未在暴露的人支气管上皮细胞中检测到突变 到一氧化二氮。

Five families of activated protooncogenes, ras, raf, jun, erbB-2, and myc so far have 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. Human bronchial epithelial cells have been neoplastically transformed with Ha-ras oncogene. Whereas the expression of the activated ras gene is not necessary for in vitro growth of the cells, Ha-ras expression is associated with a selective growth advantage in vivo. An inverse correlation of steady state thrombospondin mRNA and protein expression with malignant progression of oncogene (Ha-, k- and N-ras)-transformed human bronchial epithelial cells has been observed. Dysregulation of the G1 checkpoint in the cell cycle may lead to neoplastic transformation. Overexpression of transfected cyclin D1 gene in human esophageal cells leads to enhanced growth to the negative growth factor, TGF-beta1. Genomic instability in human bronchial epithelial cells is induced by transfection of protein phoshatase genes, cdc25A or cdc25B. In contrast, genomic instability or mutations were not detected in human bronchial epithelial cells exposed to nitric oxide.