title: Transforming growth factor-beta overrides the adhesion requirement for surface expression of alpha(5)beta(1) integrin in normal rat kidney fibroblasts. A necessary effect for induction of anchorage-independent growth.
abstract: We have previously shown that the expression of alpha(5)beta(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(5)beta(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(5)beta(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(5)beta(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(5)beta(1) integrin in NRK cells, and this effect is necessary for the induction of anchorage-independent growth.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Dalton
authors.forename: E
authors.initials: E
authors.lastname: Scharf
authors.forename: G
authors.initials: G
authors.lastname: Davey
authors.forename: R K
authors.initials: RK
authors.lastname: Assoian
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D002453:Cell Cycle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017469:Receptors, Fibronectin / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D005353:Fibronectins; D017469:Receptors, Fibronectin; D016212:Transforming Growth Factor beta