title: Response of FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene to differentiation induction by N,N-dimethylformamide.
abstract: Treatment of chemically transformed fibroblasts with N,N-dimethylformamide (DMF) results in the restoration of a nontransformed phenotype. In an attempt to identify more precisely the mechanisms by which DMF reverses the transformed phenotype, the effects of DMF on fibroblasts which were transformed by a single gene--specifically a synthetic epidermal growth factor (EGF) gene or the Ha-ras oncogene--were examined. The constitutive expression of either the Ha-ras oncogene or the EGF gene in FR3T3 fibroblasts resulted in cellular transformation. The effect of the differentiation-inducing agent DMF on several properties of these transformed cell lines was examined. The EGF-transfected cells were much more responsive to DMF than the ras-transfected cells. DMF treatment of the EGF-transfected cells resulted in the inhibition of anchorage-independent growth, the restoration of a normal cellular morphology and growth rate in monolayer culture, and the down-regulation of the proliferation-associated nucleolar protein B23. DMF treatment had a much slighter effect on growth of the ras-transfected cells in monolayer culture or under anchorage-independent growth conditions. The high proliferation rate of the ras-3 cells was associated with elevated expression of protein B23. The 19-3 cells, but not the ras-3 cells, expressed cell-surface fibronectin. Treatment of the ras-3 cells with DMF did not restore fibronectin expression. The binding of EGF was increased 3-fold in the EGF-transfected cells and decreased 20-fold in ras-transfected cells, but in neither case did DMF alter EGF binding. DMF treatment increased the secretion of EGF in the 2 transfected lines as well as in control cells. These results suggest that the aberrant-growth control in the EGF-transfected cells, but not in the ras-transfected cells, could be modulated by DMF and that the aberrant-growth control mechanisms were different in these 2 cell types.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: A E
authors.initials: AE
authors.lastname: Levine
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarty
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004126:Dimethylformamide / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D011905:Genes, ras; D066298:In Vitro Techniques; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D005353:Fibronectins; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D004815:Epidermal Growth Factor; D004126:Dimethylformamide; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)