Induction of mouse mammary tumours 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.