Transforming growth factor β1 suppresses transformation in hepatocytes by regulating α1β1 integrin expression

Academic Article

Abstract

  • We previously reported that (a) treatment of the ras-transformed hepatocyte cell line NR4 with transforming growth factor (TGF) β1 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 α1 integrin RNA than the immortalized CWSV1 cells; and (c) TGF-β1 treatment of NR4 cells stimulated the expression of α1 and β1 integrin RNAs. In this report, the role of the α1β1 integrin in TGF- β1-mediated suppression of the ras-transformed phenotype was investigated. We determined that (a) the cell surface integrin that increased in response to TGF-β1 treatment of NR4 cells was α1 integrin; (b) TGF-β1 altered the ability of NR4 cells to attach to collagen and laminin, the extracellular matrix components that interact with the α1β1 integrin receptor; (c) TGF- β1 treatment resulted in relocalization of the α1 integrin on the NR4 cell surface; and (d) TGF-β1-mediated inhibition of anchorage-independent growth was blocked by the presence of α1 integrin antibody. A cell line that overexpresses α1 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. We conclude that functional α1β1 integrin is necessary for TGF-β1-mediated suppression of the ras- transformed phenotype in the ras-transformed hepatocyte cell line NR4.
  • Author List

  • Serra R; Carbonetto S; Lord M; Isom HC
  • Start Page

  • 509
  • End Page

  • 517
  • Volume

  • 5
  • Issue

  • 5