Control of fibronectin receptor expression by fibronectin: antisense fibronectin RNA downmodulates the induction of fibronectin receptor by transforming growth factor beta1.
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.
Rajagopal
S
S
Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Huang
S
S
Albitar
M
M
Chakrabarty
S
S
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000096:biosynthesis* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D017469:Receptors, Fibronectin / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D005353:Fibronectins; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta