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 language||English (US)|
|Number of pages||10|
|Journal||International journal of oncology|
|State||Published - Aug 1996|
- Growth factors
ASJC Scopus subject areas
- Cancer Research