Rajagopal S, Huang S, Albitar M, Chakrabarty S
Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Cell Physiol. 1997 Feb;170(2):138-44. doi: 10.1002/(SICI)1097-4652(199702)170:2<138::AID-JCP5>3.0.CO;2-P.
The results of our previous studies of mouse embryo fibroblasts showed that fibronectin expression and fibronectin receptor expression are tightly coregulated and that fibronectin modulates expression of its receptor in response to treatment with the differentiation-inducing agent N,N,-dimethylformamide (Varani and Chakrabarty, 1990, J. Cell. Physiol., 143:445-454; Huang et al., 1994, J. Cell. Physiol., 161:470-482). We also found that transforming growth factor beta1 (TGFbeta1) induces a more differentiated phenotype in the epithelium-derived human colon carcinoma cell line Moser and upregulates the expression of both fibronectin and its receptor (Huang and Chakrabarty, 1994, Int. J. Cancer, 57:742-746). By expressing antisense fibronectin RNA in Moser cells, we have downregulated fibronectin mRNA expression and thus blocked the ability of TGFbeta1 to induce fibronectin expression (Huang and Chakrabarty, 1994, J. Biol. Chem., 269:28764-28768). In this study, we examined the effect of antisense fibronectin RNA expression on the induction of fibronectin receptor by TGFbeta1 and tested the hypothesis that the induction of fibronectin expression by TGFbeta1 is required for the induction of fibronectin receptor expression. Blocking fibronectin induction by TGFbeta1 attenuated the ability of TGFbeta1 to upregulate the expression of cell-surface fibronectin receptors, alpha5beta1 integrin expression, and adhesion to extracellular matrix fibronectin. We therefore conclude that induction of fibronectin expression is required for optimal upregulation of fibronectin receptor expression by TGFbeta1.
我们之前对小鼠胚胎成纤维细胞的研究结果表明，纤连蛋白表达和纤连蛋白受体表达受到紧密的共同调节，并且纤连蛋白会响应分化诱导剂N，N-二甲基甲酰胺的处理来调节其受体的表达（瓦拉尼和恰克拉巴蒂，1990年，《细胞生理学杂志》，143:445 - 454；黄等人，1994年，《细胞生理学杂志》，161:470 - 482）。我们还发现，转化生长因子β1（TGFβ1）在上皮来源的人结肠癌细胞系莫泽中诱导出更分化的表型，并上调纤连蛋白及其受体的表达（黄和恰克拉巴蒂，1994年，《国际癌症杂志》，57:742 - 746）。通过在莫泽细胞中表达反义纤连蛋白RNA，我们下调了纤连蛋白mRNA表达，从而阻断了TGFβ1诱导纤连蛋白表达的能力（黄和恰克拉巴蒂，1994年，《生物化学杂志》，269:28764 - 28768）。在本研究中，我们检测了反义纤连蛋白RNA表达对TGFβ1诱导纤连蛋白受体的影响，并检验了TGFβ1诱导纤连蛋白受体表达需要先诱导纤连蛋白表达这一假说。通过TGFβ1阻断纤连蛋白诱导减弱了TGFβ1上调细胞表面纤连蛋白受体表达、α5β1整合素表达以及对细胞外基质纤连蛋白黏附的能力。因此，我们得出结论，TGFβ1要实现纤连蛋白受体表达的最佳上调需要诱导纤连蛋白表达。
