Heparin-treated, v-myc-transformed chicken heart mesenchymal cells assume a normal morphology but are hypersensitive to epidermal growth factor (EGF) and brain fibroblast growth factor (bFGF); cells transformed by the v-Ha-ras oncogene are refractory to EGF and bFGF but are hypersensitive to insulin-like growth factors.

Chicken heart mesenchymal cells do not proliferate in culture medium containing heat-defibrinogenated plasma but proliferate briskly when incubated with epidermal growth factor (EGF) or brain fibroblast growth factor (bFGF) plus insulin-like growth factors (IGFs) or when infected with sarcoma or erythroblastosis viruses. When infected with the retrovirus MC29, which bears a v-myc oncogene, chicken heart mesenchymal cells proliferate at a more modest rate and become morphologically transformed. Heparin at 25 microgram/ml causes these MC29-transformed cells to become proliferatively quiescent and to assume a normal morphology. Heparin-treated MC29-infected cells are, however, 100 times more sensitive to EGF than are their normal, uninfected counterparts. MC29-infected cells appear, likewise, to be hypersensitive to bFGF and to PDGF preparations but not to insulin. We hypothesize, therefore, (i) that heparin prevents the generation by cells of a mitogen from plasma protein precursors in the culture medium; (ii) that the v-myc oncogene renders cells hypersensitive to EGF, bFGF, PDGF, and the putative plasma-protein-derived mitogen; and (iii) that MC29-infected cells must proliferate in order to manifest the transformed morphology. Chicken heart mesenchymal cells infected with a recombinant spleen necrosis virus containing a v-ras oncogene are morphologically transformed but proliferate only sluggishly in plasma-containing medium without added mitogenic hormones. Heparin does not significantly affect their behavior. They are refractory to mitogenic stimulation by EGF or bFGF suggesting that ras proteins mediate the effects of receptors for these hormones. The SNV/v-ras-infected cells proliferate briskly, however, in response to hyperphysiological concentrations of insulin, an IGF surrogate, and are considerably more sensitive to this IGF mitogenicity than are their normal, uninfected counterparts.