PHENOTYPIC CHANGES INDUCED BY WILD-TYPE AND VARIANT C-SRC GENES CARRYING C-TERMINAL SEQUENCE ALTERATIONS

We previously reported the isolation of PR2257, a novel avian sarcoma retrovirus which transduced the c-src protooncogene. The v-src gene of PR2257 differs from the c-src gene by a sequence change after amino a cid 525, resulting in the replacement of tyrosine 527 by a valine, and an extension of the open reading frame into the non coding region of c-src. We investigated the respective roles of Tyr527 mutation and of the C-terminal extension in activating the oncogenic properties of c-s rc. Therefore we overexpressed the wild type c-src gene and c-src vari ants, carrying either a substitution of tyrosine 527 or an extension o f the C-terminus or both modifications in combination, in chicken embr yo fibroblasts and post mitotic neuroretina (NR) cells, using replicat ion defective retroviruses. We also used in vivo inoculation of plasmi d DNA to assess the tumorigenicity of the various c-src genes, We repo rt that, in contrast to previous results, overexpression of c-src is s ufficient to induce NR cell division, While mutation of tyrosine 527 a lone significantly activates c-src transforming and tumorigenic proper ties, its combination with the C-terminal extension of PR2257 confers to this gene full oncogenic properties and increased metastatic potent ial as compared to the v-src of Rous sarcoma virus strains.