ENDOGENOUS C-SRC AS A DETERMINANT OF THE TUMORIGENICITY OF SRC ONCOGENES

We have compared the tumorigenicity of two src oncogenes, v-src and c- src(527), whose respective protein products pp60(v-src) and pp60(c-src (527)) show a different spectrum of amino acid substitutions vis-a-vis the c-src protooncogene-encoded product pp60(c-src). Whereas the exte nt of primary tumor growth induced by c-src(527) was quite similar in the two chicken lines tested, the extent of v-src-induced tumor growth showed a marked line dependence, As examined with a line of chickens that shows immune-mediated regression of v-src-induced tumors, a weake r tumor immunity, as correlated with a greater level of primary tumor growth, resulted from inoculation of c-src(527) DNA than of v-src DNA, These observations indicated that the v-src-specific amino acid subst itutions define a major tumor antigenicity, That a separate src-associ ated antigenicity is also targetable by the tumor immune response foll owed from the finding that the level of protective immunity against th e growth of c-src(527) DNA-induced tumors was augmented under conditio ns of the prior regression of v-src DNA-induced tumors, As this latter antigenicity may include one or more c-src(527)-encoded peptides that are equivalent to c-src-encoded self peptides, these observations sug gest that a host tolerance to pp60(c-src) can be broken so as to permi t a tumor immune response based on recognition of self peptides of pp6 0(c-src(527)).