Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium

Several Wnt genes are expressed in the postnatal mouse mammary gland and ar e thought to be involved in mammary gland development. Ectopic expression o f Wnt-1, which is not normally expressed in the mammary gland, drives the f ormation of a pre-neoplastic hyperplasia, Cell culture-based assays have sh own that Wnt-1 and some mammary-expressed Wnts transform C57MG cells. This has led to the suggestion that Wnt-1 functions as an oncogene through the i nappropriate activation of developmental events that are normally controlle d by the 'transforming' class of Wnts. In this study, Wnt-7b was expressed in vivo using recombinant retroviruses, Wnt-7b did not alter normal mammary gland development despite having similar effects to Wnt-1 in cell culture. We conclude that the in vitro classification of Wnts as 'transforming' doe s not correlate with the transformation in vivo. To facilitate the analysis of Wnt-expression, a lacZ-containing, bicistronic recombinant retrovirus w as developed. Immunohistochemistry and electron microscopy identified retro virally transduced myoepithelial and luminal epithelial cells in normal and hyperplastic tissues. The distribution of transduced cells in mammary outg rowths was consistent with current models of mammary stem cell identity.