Abstract
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 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.
Highlights
SUMMARY Mammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer
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
During breast tumorigenesis, mammary ductal dysplasia is observed in precancerous lesions and earlystage breast cancers
Summary
Mammary ductal dysplasia is observed in precancerous lesions and earlystage breast cancers. Because studies using genetically engineered mice have been designed to examine phenotypes caused by the functions of their target genes and these studies could not provide knowledge about the relationships between the factors involved, these models are not suitable to elucidate the molecular mechanism by which mammary ductal dysplasia is naturally formed. To understand such a mechanism of dysplasia formation, a mouse model that forms dysplasia by physiological factor(s) and facilitates the mechanistic understanding of dysplasia formation is required
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
