Stimulation of DNA Synthesis by Interferon and Transforming Growth Factor β in EL2 Rat Fibroblasts. Role of This Effect on the Expression of an EL2-Transformed Phenoptype

Abstract

The proliferation of normal cells is regulated by both positive and negative growth-effects, induced by growth-stimulatory factors [e.g., Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EGF)] and growth-inhibitory factors [e.g., Interferons (IFNs), Transforming Growth Factor β (TGFβ), Tumor Necrosis Factor (TNF)]. To investigate these effects, we analyzed DNA synthesis in an euploid fibroblast line (EL2), recently isolated from rat embryo, stimulated with EGF and treated with TGFβ and IFN respectively. Our results show that, in opposition to what is described for other fibroblast lines, in EL2 cells the treatment with appropriate concentrations of TGFβ or IFN did not inhibit the [3H]-thymidine incorporation induced by EGF, but, on the contrary, EGF-induced DNA synthesis was greatly stimulated by the presence of TGFβ or IFN in our cell cultures. The implications of these findings for elucidating the cellular events leading to the malignant conversion are discussed.