STUDIES ON THE ACTIVATED FORM OF THE HUMAN PROTO-ONCOGENE, C-HA-RAS

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We have transfected various viral and cellular oncogenes into primary cultures of rat embryo cells and have obtained lines of morphologically transformed cells. Transformation with the ras oncogene alone was observed; however, a 10-fold increase in the transformation frequency was obtained when ras was cotransfected with the adenovirus E1A gene. We have examined cell lines transformed by the ras oncogene alone, and by ras plus E1A and have observed a striking difference in their metastatic potential as assayed in nude mice. Specifically, the ras alone transformants are highly metastatic, while the two gene transformants show a very low metastatic potential. Transfection of serotype 2 E1A gene, but not the serotype 12 E1A gene, into the ras alone transformants results in a substantial reduction (at least 10-fold) in the metastatic potential of these cell lines. Experiments are in progress to investigate the mechanism by which the adenovirus type 2 E1A gene reduces the metastatic potential of the ras alone transformants. In addition, we have constructed two cDNA libraries from both a high metastatic and a low metastatic cell line. These libraries will be screened with cDNA probes in order to isolate genes that are uniquely or preferentially expressed in either cell line.