Tumor promoters alter gene expression and protein phosphorylation in avian cells in culture.

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Abstract
The effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the synthesis and modification of polypeptides was studied in normal avian [chicken embryonic fibroblasts] cells and cells infected by wild-type and temperature-sensitive Rous sarcoma virus (RSV). Using 2-dimensional gel electrophoresis, alterations in the abundance of cellular polypeptides and in their phosphorylation that seem unique to TPA treatment were detected. The state of phosphorylation of the major putative substrate for the action of the src gene-associated protein kinase, the 34-36 kdalton protein, was not altered. Examination of the phosphorylated amino acid content of total cellular phosphoproteins revealed that the response to TPA was not associated with detectable increases in their phosphotyrosine content. These results make it unlikely that TPA acts by the activation of the phosphorylating activity of the cellular proto-src gene or by the activation of other cellular phosphotyrosine-specific kinases. Temperature-sensitive RSV-infected cells at a nonpermissive temperature demonstrate an increased sensitivity to TPA treatment. Apparently this is not due to reactivation of the phosphorylating activity of the defective src gene product or to its leakiness, lending support to the notion of multistep viral carcinogenesis.