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J Biol Chem, Vol. 274, Issue 42, 30139-30145, October 15, 1999

Transforming Growth Factor-beta Overrides the Adhesion Requirement for Surface Expression of alpha 5beta 1 Integrin in Normal Rat Kidney Fibroblasts
A NECESSARY EFFECT FOR INDUCTION OF ANCHORAGE-INDEPENDENT GROWTH

Stephen L. Dalton, Eric Scharf, Gabriela Davey, and Richard K. Assoian

From the Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084

We have previously shown that the expression of alpha 5beta 1 integrin on the cell surface is dependent upon cell adhesion to the extracellular matrix, and we report here that transforming growth factor-beta (TGF-beta ) overcomes this requirement in normal rat kidney (NRK) fibroblasts. Thus, suspended NRK cells treated with TGF-beta show levels of surface alpha 5beta 1 integrin that are equivalent to those seen in adherent cells. Moreover, several experiments showed that this effect is necessary for the induction of anchorage-independent growth by TGF-beta . First, a kinetic analysis showed that surface expression of alpha 5beta 1 integrin was restored in TGF-beta -treated NRK cells prior to the induction of anchorage-independent growth. Second, NRK cell mutants that have lost their TGF-beta requirement for surface expression of alpha 5beta 1 integrin were anchorage-independent in the absence of TGF-beta . Third, an antisense oligonucleotide to the beta 1 integrin subunit or, fourth, stable expression of an alpha 5-antisense cDNA blocked the ability of TGF-beta to stimulate anchorage-independent growth. Thus, TGF-beta overrides the adhesion requirement for surface expression of alpha 5beta 1 integrin in NRK cells, and this effect is necessary for the induction of anchorage-independent growth.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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