The human cellular homolog (c-mos-Hu) of the Moloney murine sarcoma virus (MSV) transforming sequence, v-mos, could be activated to express a transforming potential in NIH3T3 mouse fibroblasts. Linkage of the MSV-dervived long terminal repeat (LTR) sequences approximately 50 base pairs 5' to the start of the conserved mos open reading frame allowed c-mos-Hu to transform NIH3T3 cells at a low efficiency (approximately 150 focus-forming units/p mole). Cells transformed by c-mos-Hu were tumorigenic in nude mice and expressed high levels of a 33,000 dalton protein recognized by human mos-specific antisera and broadly reactive anti-v-mos sera in both immunoprecipitation and Western blot analysis. These results indicated that the transforming potential of mos-related cellular sequences has been conserved between mouse and man. The genetic lesion responsible for the activation of an N-ras sequence isolated from a human gastric adenocarcinoma has been identified. A single base change in the 61st codon results in the substitution of an arginine for glutamine at this position, resulting in an activated N-ras product abel to transform NIH3T3 cells. No biological activity could be detected in DNA from EBV immortalized lymphocytes prepared from the same individual. Utilizing a nude mouse tumor assay to screen for transfectable oncogenes, transforming sequences have been detected in DNA from human ovarian carcinoma-derived cell lines and from an MuLV-induced mouse lymphoma. The ovarian carcinoma-derived transforming sequences do not appear to be related to the known human ras family of oncogenes. The mouse lymphoma-derived sequence appears to be a murine H-ras sequence.
