NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS BY ONCOGENES OR CARCINOGENS

ras、raf、jun、erbB-2和myc五个活化原癌基因家族 迄今为止与人支气管癌有关。 人类 体外培养的支气管上皮细胞被用于研究 这些特定的癌基因和生长调节基因的功能作用 在致癌和肿瘤进展中的作用。 人支气管上皮 细胞已经被Ha-ras癌基因肿瘤转化。 而 激活的ras基因的表达对于体外培养不是必需的， Ha-ras表达与细胞的选择性生长有关。 体内生长优势。 稳态的逆相关 血小板反应素mRNA和蛋白表达与恶性肿瘤进展的关系 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 可能导致肿瘤转化。 过表达转染的 人食管细胞中的细胞周期蛋白D1基因导致食管癌细胞的生长增强， 负生长因子TGF-β 1。 人类基因组不稳定性 支气管上皮细胞通过转染蛋白质诱导 磷酸酶基因cdc 25 A或cdc 25 B。 相反，基因组不稳定性或 在暴露的人支气管上皮细胞中未检测到突变， 到一氧化氮。

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.