Interactions Between C-Myc and Development in Mammary Carcinogenesis

摘要

The purpose of the research funded by this award is to identify molecular interactions between the c-MYC proto-oncogene and normal mammary developmental events. Ultimately, our goal is to identify how these interactions affect the process of mammary carcinogenesis. To this end, we seek to identify mammary development stage specific effects of aberrant c-MYC activation, to identify molecular mechanisms accounting for these effects, and to determine what role these interactions plays in mediating the biological effects of aberrant c-MYC expression within the mammary epithelium. This work has led to the finding that aberrant c-MYC activation for discrete periods during early and late pregnancy has dramatically different outcomes. Specifically, c-MYC activation during late pregnancy results in premature Stat5 activation followed by precocious lactation, whereas c-MYC activation during early pregnancy results in neither of these dramatic phenotypes. We are now in the process of determining what role c-MYC-induced activation of the Stat5 mammary developmental signaling pathway plays in mediating the effects of aberrant activation of c-proliferation, differentiation, apoptosis, and tumorigenesis.