CONTROL OF FIBRONECTIN RECEPTOR EXPRESSION BY FIBRONECTIN - ANTISENSEFIBRONECTIN RNA DOWN-MODULATES THE INDUCTION OF FIBRONECTIN RECEPTOR BY TRANSFORMING GROWTH-FACTOR-BETA-1

The results of our previous studies of mouse embryo fibroblasts showed that fibronectin expression and fibronectin receptor expression are t ightly coregulated and that fibronectin modulates expression of its re ceptor in response to treatment with the differentiation-inducing agen t N,N,-dimethylformamide (Varani and Chakrabarty, 1990, J. Cell. Physi ol., 143:445-454; Huang et al., 1994, J. Cell. Physiol., 167:470-482). We also found that transforming growth factor beta 1 (TGF beta 1) ind uces a more differentiated phenotype in the epithelium-derived human c olon carcinoma cell line Moser and upregulates the expression of both fibronectin and its receptor (Huang and Chakrabarty, 1994, Int. J. Can cer, 57:742-746). By expressing antisense fibronectin RNA in Moser cel ls, we have downregulated fibronectin mRNA expression and thus blocked the ability of TGF beta 1 to induce fibronectin expression (Huang and Chakrabarty, 1994, J. Biol. Chem., 269:28764-28768). In this study, w e examined the effect of antisense fibronectin RNA expression on the i nduction of fibronectin receptor by TGF beta 1 and tested the hypothes is that the induction of fibronectin expression by TGF beta 1 is requi red for the induction of fibronectin receptor expression. Blocking fib ronectin induction by TGF beta 1 attenuated the ability of TGF beta 1 to upregulate the expression of cell-surface fibronectin receptors, al pha 5 beta 1 integrin expression, and adhesion to extracellular matrix fibronectin. We therefore conclude that induction of fibronectin expr ession is required for optimal upregulation of fibronectin receptor ex pression by TGF beta 1. (C) 1997 Wiley-Liss, Inc.