title: Resistance to TGF beta in SV40 large T-immortalized rat intestinal epithelial cells is associated with down-regulation of TGF beta type I receptor.
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 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.
authors.affiliation: HOP ST ANTOINE,INSERM U55,EPITHELIUM GASTROINTESTINAL,EQUIPE CANC & DIFFERENCIAT,F-75571 PARIS 12,FRANCE. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MCGILL UNIV,DEPT SURG,DIV UROL,MONTREAL,PQ H3G 1A4,CANADA. MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mahida
authors.forename: S
authors.initials: S
authors.lastname: Djelloul
authors.forename: A
authors.initials: A
authors.lastname: Atfi
authors.forename: C
authors.initials: C
authors.lastname: Ciacci
authors.forename: M
authors.initials: M
authors.lastname: Debeaumont
authors.forename: S
authors.initials: S
authors.lastname: Chevalier
authors.forename: C
authors.initials: C
authors.lastname: Gespach
authors.forename: D
authors.initials: D
authors.lastname: Podolsky