Autocrine transforming growth factor β1 modulates the expression of integrin α5β1 in human colon carcinoma FET cells

D. Wang, G. H. Zhou, T. M. Birkenmeier, J. Gong, L. Sun, M. G. Brattain

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Transforming growth factor β (TGF-β) has been extensively studied as an exogenous agent that stimulates the expression of extracellular matrix proteins and their cell-surface integrin receptors in a variety of cell types. However, the recent demonstration of autocrine TGF-β growth effects in a number of cell types suggests that the steady-state expression of extracellular matrix and integrin proteins and their biological activity may also be under autocrine TGF-β control. Previously, we reported that repression of autocrine TGF-β1 activity by constitutive expression of a full-length TGF-β1 antisense cDNA led to abrogation of autocrine negative TGF-β and, as a result, increased tumorigenicity and anchorage-independent growth of a poorly tumorigenic, well-differentiated colon carcinoma cell line designated FET (Wu, S., Theodorescu, D., Kerbel, R. S., Willson, J. K. V., Mulder, K. M., Humphrey, L. E., and Brattain, M. G. (1992) J. Cell Biol. 116, 187-196). Consequently, we have used this model system to study the effects of repression of autocrine TGF-β1 activity on the expression of integrin α5β1 and integrin α5β1-mediated cell adhesion to fibronectin. The expression of the integrin α5 subunit was reduced in TGF-β1 antisense transfected FET cells at both mRNA and protein levels as determined by RNase protection assays and immunoprecipitation, respectively. Autocrine TGF-β1 had no effect on the transcription of integrin α5 and β1 subunits, indicating that autocrine TGF-β1 may regulate integrin α5β1 expression at the post-transcriptional level. The diminished expression of integrin α5β1 on the cell surface led to the reduced adhesion of TGF-β1 antisense transfected cells to fibronectin. This phenomenon could be reversed by treatment with exogenous TGF-β1.

Original languageEnglish
Pages (from-to)14154-14159
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number23
DOIs
StatePublished - Jan 1 1995

    Fingerprint

Cite this