CYTOSKELETAL PROTEINS IN ONCOGENIC TRANSFORMATION AND HUMAN NEOPLASIA

我们正在研究肿瘤转化和 原肌球蛋白表达或利用的生化紊乱 (TMS)。在NIH/3T3成纤维细胞中，由一些相关的和 不相关的逆转录病毒癌基因，转化的表型表达 与抑制两个特定TM的合成相关 异构体(“肌肉型”)。在所有可以在二维图像上检测到的蛋白质中 全细胞蛋白质的凝胶电泳，只有TMS在这一过程中表现出来 道路。肿瘤生长因子-α对大鼠成纤维细胞的作用 (转化生长因子-α)，除了诱导转化表型外， 特异性地抑制肌型TM的合成，并抑制其 利用细胞骨架，加强细胞与细胞之间的联系 TM的抑制和转化表型的表达及添加 癌基因自分泌途径在生化水平上的支持 行动。研究结果指出， 表皮生长因子受体激活与微丝 组织。原肌球蛋白表达与癌基因表达的关系 肿瘤在小鼠和人类的上皮细胞系统中被研究。在……里面 Ha-ras癌基因转化的小鼠乳腺上皮细胞 在细胞骨架中积累的TM与肌动蛋白的比率降低， 表明TM缺乏微丝的产生。《The TM》 正常二倍体人乳腺上皮细胞表达的亚型有 与乳腺癌细胞株的表达模式进行了比较。 特定TM亚型的表达缺陷在所有的 对乳腺癌细胞株的研究表明，错乱可能起到了作用 TM在人类肿瘤中的表达。

We are examining the relationship between neoplastic transformation and biochemical derangements of expression or utilization of tropomyosins (TMs). In NIH/3T3 fibroblasts transformed by a number of related and unrelated retroviral oncogenes, expression of the transformed phenotype was reproducibly correlated with suppression of synthesis of two specific TM isoforms ("muscle type"). Of all the proteins detectable on two-dimensional gel electrophoresis of whole-cell proteins, only the TMs behaved in this way. Treatment of rat fibroblasts with tumor growth factor-alpha (TGF-alpha), in addition to inducing the transformed phenotype, specifically suppressed synthesis of muscle-type TMs and inhibited their utilization in the cytoskeleton, strengthening the connection between suppression of TM and expression of the transformed phenotype and adding support at the biochemical level for an autocrine pathway in oncogene action. The findings point out the close biochemical relationship between epidermal growth factor (EGF) receptor activation and microfilament organization. Tropomyosin expression in relation to oncogene expression and neoplasia is being studied in murine and human epithelial cell systems. In mouse mammary epithelial cells transformed by the Ha-ras oncogene, the ratio of TM to actin accumulating in the cytoskeleton was reduced, indicating the production of microfilaments deficient in TM. The TM isoforms expressed by normal diploid human mammary epithelial cells have been compared with the pattern expressed by breast carcinoma cell lines. Defects in expression of particular TM isoforms occurred in all of the breast carcinoma cell lines studied, suggesting a possible role of deranged TM expression in human neoplasia.