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

Autor: Y, Mahida, S, Djelloul, A, Atfi, C, Ciacci, M, Debeaumont, S, Chevalier, C, Gespach, D, Podolsky
Rok vydání: 2011
Zdroj: International journal of oncology. 9(2)
ISSN: 1019-6439
Popis: 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 TGF beta 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 TGF alpha and TGF beta. However, despite a marked increase in TGF beta-stimulated p78 kinase activity observed in ESKI-1 and IEC cells, TGF beta did not modulate growth, or extracellular matrix expression in ESKI-1 cells. Resistance to growth modulation was associated with downregulation of TGF beta. Type I receptor expression in the SV40 large T-immortalized cells. Thus, proliferative resistance to TGF beta inhibition can result from depletion of the TGF beta type I receptor and disruption of the TGF beta 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.
Databáze: OpenAIRE