title: Ras, but not Src, transformation of RIE-1 epithelial cells is dependent on activation of the mitogen-activated protein kinase cascade.
abstract: Src transformation of NIH3T3 mouse fibroblasts has been shown to be dependent on Ras function. Since we recently showed that the signaling pathways that mediate Ras transformation of RIE-1 rat intestinal epithelial cells are distinct from those that cause Ras transformation of fibroblasts, we utilized three approaches to determine if Src transformation of RIE-1 cells is dependent on Ras. First, although both Ras and Src cause upregulation of an epidermal growth factor (EGF) receptor-dependent autocrine growth loop, only Ras transformation required this activity. Second, whereas both Src and Ras caused upregulation of the p42 and p44 mitogen-activated protein kinases (MAPKs), only Ras transformation was blocked by the inhibition of MAPK activation by treatment with the PD 98059 MEK inhibitor. Third, treatment with the farnesyltransferase inhibitor FTI-277 blocked Ras, but not Src, transformation. Taken together, these observations suggest that Src transformation of RIE-1 cells is not dependent on Ras. Finally, we determined that Ras activation of Raf-independent pathways alone is sufficient to cause growth transformation of RIE-1 cells. Thus, both Ras and Src cause transformation of RIE-1 cells via pathways distinct from those required to cause transformation of NIH3T3 cells.
authors.affiliation: Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Oldham
authors.forename: A D
authors.initials: AD
authors.lastname: Cox
authors.forename: E R
authors.initials: ER
authors.lastname: Reynolds
authors.forename: N S
authors.initials: NS
authors.lastname: Sizemore
authors.forename: R J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: C J
authors.initials: CJ
authors.lastname: Der
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D051231:Farnesyltranstransferase; D011905:Genes, ras; D016391:Genes, src; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009154:Mutation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; C096856:FTI 277; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases