Control of AKR fibroblast phenotype by fibronectin: Regulation of cell‐surface fibronectin binding receptor by fibronectin

Shuang Huang, James Varani, Subhas Chakrabarty

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Results of previous studies show that the expression of fibronectin and its cell‐surface fibronectin binding receptor is coregulated in 3‐methylchloranthrene transformation of normal AKR‐2B cells to form AKR‐MCA cells and in N, N,‐dimethylformamide (DMF) induction of differentiation of transformed AKR‐MCA cells (1990, J. Cell. Physiol., 143:445). In this study, we tested the corgulation hypothesis by transfection experiments using an antisense fibronectin expression vector. We determined the effect of antisense fibronectin RNA expression on untransformed AKR‐2B cells, and on the responses of transformed AKR‐MCA cells to DMF treatment. Expression of antisense fibronectin RNA in AKR‐2B cells down‐modulated fibronectin production, reduced adhesion to extracellular fibronectin, and altered cellular morphology Saturation binding and Scatchard analyses using radiolabelled fibronectin revealed a concurrent down‐modulation of cell‐surface fibronectin binding sites, but the binding affinity of the receptor for the ligand was not affected. Immunoblotting and immunostaining revealed down‐modulation of the expression of α5β1 integrins. Expression of antisense fibronectin RNA in AKR‐MCA cells down‐modulated the ability of DMF to restore normal fibronectin production, cell‐surface fibronectin binding receptor, adhesion to extracellular fibronectin, and cellular morphology. These studies show that both fibronectin and its cell‐surface fibronectin binding receptor were tightly regulated during transformation and induction of differentiation in these cells, that the ligand and its cell‐surface fibronectin binding receptor worked together to bring about phenotypic changes, and that fibronectin production regulated the expression of its cell‐surface fibronectin binding receptor. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)470-482
Number of pages13
JournalJournal of Cellular Physiology
Volume161
Issue number3
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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