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 pp60v-src and pp60c-src(527) show a different spectrum of amino acid substitutions vis-à-vis the c-src protooncogene-encoded product pp60c-src. Whereas the extent 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 weaker 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 substitutions define a major tumor antigenicity. That a separate src-associated antigenicity is also targetable by the tumor immune response followed from the finding that the level of protective immunity against the growth of c-src(527) DNA-induced tumors was augmented under conditions 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 suggest that a host tolerance to pp60c-src can be broken so as to permit a tumor immune response based on recognition of self peptides of pp60c-src(527).
Halpern
M S
MS
Department of Pathology and Laboratory Medicine, Medical College of Pennsylvania, Philadelphia, USA.
England
J M
JM
Kopen
G C
GC
Christou
A A
AA
Taylor
R L
RL
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D002645:Chickens; D016391:Genes, src; D007109:Immunity; D008285:Major Histocompatibility Complex; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics* / Q000276:immunology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000276:immunology
D000951:Antigens, Neoplasm; D015688:Oncogene Protein pp60(v-src); D016392:Proto-Oncogene Proteins pp60(c-src)