Resistance to TGFβ in SV40 large T-immortaIized rat intestinal epithelial cells is associated with down-regulation of TGFβ type I receptor

Y. R. Mahida, S. Djelloul, A. Atfi, C. Ciacci, M. Debeaumont, S. Chevalier, C. Gespach, D. K. Podolsky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

A new continuous cell line designated ESKI-1 was established by transfection of rat fetal intestinal epithelial cells with ecotropic retroviruses containing SV40 large T oncogene. The ESKI-1 cell line exhibits morphologic features of an epithelial cell line and expresses the OCI-5 and cytokeratin 8 transcripts associated with epithelial cells in the small intestine. Signal transduction and proliferation responses to TGFβ has been characterized in ESKI-1 cells, in comparison with the spontaneously-immortalized IEC cell lines originating from neonatal rat duodenum and ileum. ESKI-1 express both TGFα and TGFβ. However, despite a marked increase in TGFβ-stimulated p78 kinase activity observed in ESKI-1 and IEC cells, TGFβ did not modulate growth, or extracellular matrix expression in ESKI-1 cells. Resistance to growth modulation was associated with downregulation of TGFβ. Type I receptor expression in the SV40 large T-immortalized cells. Thus, proliferative resistance to TGFβ inhibition can result from depletion of the TGFβ type I receptor and disruption of the TGFβ signaling pathway downstream the p78 serine/threonine kinase. These molecular defects constitute two early events during the SV40LT-mediated immortalization and neoplastic progression of the intestinal epithelia.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalInternational journal of oncology
Volume9
Issue number2
StatePublished - Aug 1996

Keywords

  • Differentiation
  • Growth factors
  • Kinase
  • Oncogene
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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