Transforming growth factor beta 1 suppresses transformation in hepatocytes by regulating alpha 1 beta 1 integrin expression

Cell Growth Differ. 1994 May;5(5):509-17.

Abstract

We previously reported that (a) treatment of the ras-transformed hepatocyte cell line NR4 with transforming growth factor (TGF) beta 1 suppresses many characteristics associated with the transformed phenotype including altered morphology, actin cytoskeleton reorganization, and anchorage-independent growth such that the cells more closely resemble the immortalized CWSV1 parent cell line; (b) transformed NR4 cells expressed significantly less alpha 1 integrin RNA than the immortalized CWSV1 cells; and (c) TGF-beta 1 treatment of NR4 cells stimulated the expression of alpha 1 and beta 1 integrin RNAs. In this report, the role of the alpha 1 beta 1 integrin in TGF-beta 1-mediated suppression of the ras-transformed phenotype was investigated. We determined that (a) the cell surface integrin that increased in response to TGF-beta 1 treatment of NR4 cells was alpha 1 integrin; (b) TGF-beta 1 altered the ability of NR4 cells to attach to collagen and laminin, the extracellular matrix components that interact with the alpha 1 beta 1 integrin receptor; (c) TGF-beta 1 treatment resulted in relocalization of the alpha 1 integrin on the NR4 cell surface; and (d) TGF-beta 1-mediated inhibition of anchorage-independent growth was blocked by the presence of alpha 1 integrin antibody. A cell line that overexpresses alpha 1 integrin was derived from NR4 cells; characterization of these cells indicated that they continued to express H-ras RNA but were less transformed than the parent NR4 cells. Specifically, they had an altered morphology, an organized actin cytoskeleton, and reduced ability to demonstrate anchorage-independent growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Line, Transformed
  • Cell Membrane / metabolism
  • Cell Transformation, Neoplastic / drug effects*
  • Collagen / metabolism
  • Cytoskeleton / drug effects
  • Gene Expression / drug effects*
  • Genes, ras / physiology
  • Integrin alpha1beta1
  • Integrins / biosynthesis*
  • Integrins / genetics
  • Laminin / metabolism
  • Liver / cytology*
  • Liver / metabolism
  • Phenotype
  • RNA, Messenger / biosynthesis
  • Rats
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Integrin alpha1beta1
  • Integrins
  • Laminin
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Collagen