N-RAS ONCOGENE EXPRESSION CHANGES THE GROWTH-CHARACTERISTICS OF HUMAN-MELANOMA IN 2 INDEPENDENT SCID-HU MOUSE MODELS

Fifteen percent of all human melanomas carry mutations in ros genes, t he majority of which ave located in codon 61 of the N-ras gene. Howeve r, the biological significance of these mutations is as yet unknown. I n this study, we investigated the influence of N-ras oncogene products mutated in codon 61 on the growth characteristics of human melanoma i n vivo by establishing 2 SCID-hu mouse xenotransplantation models. Tum ors grown in SCID mice injected with human melanoma carrying activated N-ras genes were significantly larger (p < 0.004) than tumors grown i n animals injected with the appropriate control transfectants. Additio nally, tumors with N-ras point mutations clearly showed a more pleomor phic phenotype than the control groups. Our results, obtained in 2 ind ependent SCID-hu xenotransplantation models, suggest that mutated N-ra s oncogene expression may be an important factor influencing growth ch aracteristics of human melanoma without altering metastatic potential. These novel in vivo model systems provide a tool for further study of the biology of mutated ras in melanoma and should also prove useful f or testing new and improved treatment strategies for human melanoma ca rrying mutated ros genes.