INDUCTION OF MOUSE MAMMARY-TUMORS IN A TRANSPLANTATION SYSTEM BY THE SEQUENTIAL INTRODUCTION OF THE MYC AND RAS ONCOGENES

A novel helper-free defective retrovirus containing the v-Ha-ras oncogene has been constructed and used to introduce the gene into primary mouse mammary epithelial cells already containing the v-myc oncogene. Transplantation of such doubly altered cells into cleared mammary fat pads led to the formation of mammary tumors within 6 to 8 weeks of transplantation. In a separate experiment, both oncogenes were simultaneously introduced to normal epithelium and once again tumours were formed. Neither oncogene alone gave a significant rate of tumour formation, although myc alone gave a reproducible hyperplasia as previously reported and ras alone gave occasional dysplastic or alveolar lesions. The results presented here demonstrate the progression of a normal cell through a hyperplastic intermediate to a tumour-forming cell in a versatile in vivo transplantation model.