INDUCTION OF MAMMARY EPITHELIAL HYPERPLASIAS AND MAMMARY-TUMORS IN TRANSGENIC MICE EXPRESSING A MURINE MAMMARY-TUMOR VIRUS ACTIVATED C-SRC FUSION GENE/

Activation of the c-Src tyrosine kinase has been implicated as an impo rtant step in the induction of mammary tumors in both mice and humans. To directly assess the effect of mammary gland-specific expression of activated c-Src, we established transgenic mice that carry a constitu tively activated form of c-src under transcriptional control of the mu rine mammary tumor virus long terminal repeat. Female mice derived fro m several independent transgenic lines lactate poorly as a consequence of an impairment in normal mammary epithelial development, In additio n to this lactation defect, female mice frequently develop mammary epi thelial hyperplasias, which occasionally progress to frank neoplasias. Taken together, these observations suggest that expression of activat ed c-Src in the mammary epithelium of transgenic mice is not sufficien t for induction of mammary tumors.