Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus.

Neoplastic transformation of pigment cells in the teleostean fish Xiphophorus is mediated by a cellular oncogene (Tu). Normally. Tu is suppressed by multiple regulating genes (R). Depending on impairment and loss of R genes, Tu is permitted to express itself phenotypically. In the pigment cell system, different degrees of Tu expression lead to small spots of transformed cells or to benign or malignant melanoma. All neoplastic and nonneoplastic cells of all Xiphophorus genotypes tested thus far appear to contain the cellular homolog (c-src) of the avian sarcoma virus oncogene (v-src). The evidence for this stems from the detectability of a Mr 60,000 phosphoprotein with associated kinase activity (pp60c-src) that reacts with antiserum against viral pp60src. We followed the inheritance of Tu (identified by spots and melanomas) compared to the expression of c-src identified by the pp60c-src-associated protein kinase). By quantitative determination of kinase activity in immunoprecipitated pp60c-src from fish showing different degrees of Tu expression, we have investigated whether there exists a correlation between the expression of c-src and Tu. In genotypes with the same genetic background, cells from Tu-containing fish express more pp60c-src than do cells from fish lacking Tu. In genotypes carrying a Tu gene and which show differences in the amount of gene expression due to a different extent of repression by regulating genes, analysis of kinase activity revealed that an increase of Tu expression is correlated with an elevated level of pp60c-src-associated kinase activity. Our findings may indicate that c-src activity in Xiphophorus is modulated by the Tu gene product or that Tu and c-src are regulated coordinately.