ALTERATION OF MORPHOGENESIS BY THE V-MYC ONCOGENE IN TRANSPLANTS OF MAMMARY-GLAND

Abstract

To see if individual oncogenes can alter three-dimensional growth in vivo, we have inserted the v-myc oncogene into transplants of mouse mammary gland. Primary cultures of mammary epithelial cells were infected with helper-free retrovirus to insert v-myc oncogenes, and transplanted into cleared mammary fat pads (mammary glands from which the natural epithelium had been removed) of host mice. Uninfected transplants, and transplants infected with retrovirus constructs that carry no oncogene, grew to form an epithelial ''tree'' resembling normal mammary gland, as expected. Transplants infected with retroviruses carrying v-myc oncogenes grew to form a characteristic, abnormal (hyperplastic) pattern in which the ducts were more densely packed than normal. Integration of the retrovirus in the transplants was demonstrated. The effect of the oncogene was local, not systemic, as some transplants showed adjacent areas of normal and hyperplastic growth. Thus v-myc can alter morphogenesis without growth becoming disorganized.