摘要：SummaryMammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer. However, the mechanism of dysplasia formation remains elusive. Here we show, by establishing a novel dysplasia model system, that estrogen, a female hormone, has the potential to cause mammary ductal dysplasia. We injected estradiol (E2), the most active form of estrogen, daily into scid mice with a defect in non-homologous end joining repair and observed dysplasia formation with cell proliferation at day 30. The protooncogeneMycis a downstream target of estrogen signaling, and we found that its expression is augmented in mammary epithelial cells in this dysplasia model. Treatment with a Myc inhibitor reduced E2-induced dysplasia formation. Moreover, we found that isoflavones inhibited E2-induced dysplasia formation. Our dysplasia model system provides insights into the mechanistic understanding of breast tumorigenesis and the development of breast cancer prevention.Graphical AbstractDisplay OmittedHighlights•Excess amount of estrogen administration in scid mice induces mammary ductal dysplasia•E2-induced Myc expression is one of the causes of dysplasia formation•Progesterone and isoflavones have a potential to prevent E2-induced dysplasiaMolecular Biology; Cell Biology; Cancer
