Function-dependent cooperation between oncogene activation and nonrandom chromosome change during tumorigenic...

We determined the tumorigenicity of SHOK cells, a Syrian hamster cell line, morphologically transformed by the introduction of either c-Ha-ras, c-Ki-ras, N-ras, v-mos, v-fgr, or v-src genes. When 1 x 10(6) cells were injected subcutaneously into nude mice, SHOK cells containing one of those oncogenes gave rise to tumors within 3 weeks, while the parental SHOK cells, or SHOK cells containing the neo gene, did not show tumorigenicity even 200 days after injection. From karyotype analysis, the addition of chromosome 3 was consistently found in tumor cells derived from SHOK cells containing the c-Ha-ras, c-Ki-ras, or v-mos genes, and the acquisition of chromosome 9 was a common change observed in tumor cells derived from SHOK cells morphologically transformed by the v-fgr or v-src gene. No consistent chromosomal change was observed in tumor cells containing the N-ras gene. The results obtained from Southern blot analysis showed that amplification of introduced oncogenes was detected in the case of c-Ha-ras, c-Ki-ras, N-ras, v-fgr, and v-src genes. These results indicate that nonrandom chromosome changes, along with the amplification of introduced oncogenes, are required for the tumorigenic conversion. Our findings propose the possibility that secondary chromosomal changes associated with the tumorigenic conversion of morphologically transformed cells occur dependent on the function of the primary activated oncogene introduced.