title: Overexpression of H-ras oncogene induces resistance to the growth-inhibitory action of transforming growth factor beta-1 (TGF-beta 1) and alters the number and type of TGF-beta 1 receptors in rat intestinal epithelial cell clones.
abstract: In this report, we utilize rat intestinal cell (IEC-18) clones expressing an activated human H-ras gene to investigate the relationship between malignant transformation and growth control by transforming growth factor beta (TGF-beta). We demonstrate that clones expressing high levels of H-ras oncogene lose sensitivity to the growth inhibitory action of TGF-beta. The loss of sensitivity is related to the degree of H-ras expression and is shown to be a direct consequence of H-ras expression through the use of a clonal cell line with inducible expression of activated H-ras. Co-incident with the loss of growth inhibition, ras-expressing clones display an altered expression of TGF-beta-binding proteins as detectable by [125I]TGF-beta cross-linking. While IEC-18 cells express type II (92 kDa) binding protein predominantly, H-ras expression induces a shift to predominantly type I (69 kDa) binding protein expression.
authors.affiliation: Ontario Cancer Institute, University of Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Filmus
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: R N
authors.initials: RN
authors.lastname: Buick
mesh_terms: D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells; D015870:Gene Expression; D011905:Genes, ras; D006131:Growth Inhibitors; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016283:Proto-Oncogene Proteins p21(ras)