| First Author | Itou J | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 2 | Pages | 100821 |
| PubMed ID | 31978754 | Mgi Jnum | J:306822 |
| Mgi Id | MGI:6717657 | Doi | 10.1016/j.isci.2020.100821 |
| Citation | Itou J, et al. (2020) Estrogen Induces Mammary Ductal Dysplasia via the Upregulation of Myc Expression in a DNA-Repair-Deficient Condition. iScience 23(2):100821 |
| abstractText | Mammary 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 protooncogene Myc is 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. |
