Harvey-ras mediated neoplastic development in the mouse mammary gland.

The role of a Harvey-ras oncogene in mammary epithelial neoplasia was examined by infecting primary cultures of normal mouse mammary epithelial cells with either the Harvey murine sarcoma virus (psi 2HaMSV) alone or with HaMSV plus a helper virus. The biological effects of expression of the Ha-ras oncogene were determined by transplanting the infected cells into gland-cleared mammary fat pads of virgin Balb/c mice. Expression of the Ha-ras oncogene was correlated with the development of mammary epithelial neoplasms. Cells infected with replication-defective HaMSV alone formed dysplastic, non-invasive mammary outgrowths. Cells infected with HaMSV plus a helper virus developed poorly-differentiated, invasive mammary epithelial tumors. Uninfected cells and cells infected with only the helper virus formed normal mammary trees. Expression of the mutant viral Ha-ras p21 was detected in dysplastic outgrowths and tumors but not in normal mammary outgrowths. Use of this transgenic organ system to genetically alter epithelium of the mouse mammary gland has permitted correlation of expression of a Ha-ras oncogene with development of mouse mammary neoplasia.