Cui W, Fowlis D J, Bryson S, Duffie E, Ireland H, Balmain A, Akhurst R J
Department of Medical Genetics, Glasgow University, United Kingdom.
Cell. 1996 Aug 23;86(4):531-42. doi: 10.1016/s0092-8674(00)80127-0.
TGFbeta1 has been implicated in cell cycle control and carcinogenesis. To address the exact function of TGFbeta1 in skin carcinogenesis in vivo, mice with TGFbeta1 expression targeted to keratinocytes were subjected to long-term chemical carcinogenesis treatment. TGFbeta1 showed biphasic action during multistage skin carcinogenesis, acting early as a tumor suppressor but later enhancing the malignant phenotype. The transgenics were more resistant to induction of benign skin tumors than controls, but the malignant conversion rate was vastly increased. There was also a higher incidence of spindle cell carcinomas, which expressed high levels of endogenous TGFbeta3, suggesting that TGFbeta1 elicits an epithelial-mesenchymal transition in vivo and that TGFbeta3 might be involved in maintenance of the spindle cell phenotype. The action of TGFbeta1 in enhancing malignant progression may mimic its proposed function in modulating epithelial cell plasticity during embryonic development.
转化生长因子β1（TGFbeta1）与细胞周期控制和致癌作用有关。为了明确TGFbeta1在体内皮肤致癌过程中的具体功能，对将TGFbeta1表达靶向角质形成细胞的小鼠进行了长期化学致癌处理。TGFbeta1在多阶段皮肤致癌过程中表现出双相作用，早期作为肿瘤抑制因子起作用，但后期会增强恶性表型。转基因小鼠比对照小鼠对良性皮肤肿瘤的诱导更具抗性，但恶性转化率大幅增加。梭形细胞癌的发生率也更高，这些肿瘤表达高水平的内源性TGFbeta3，这表明TGFbeta1在体内引发上皮-间质转化，并且TGFbeta3可能参与维持梭形细胞表型。TGFbeta1在增强恶性进展中的作用可能类似于其在胚胎发育过程中调节上皮细胞可塑性的假定功能。
