The Role of Myoepithelium in Mammary Development and Tumorigenesis
Abstract
The focus of our USAMRMC sponsored investigations is the study of mammary myoepithelial cell function and the role of these cells in regulating glandular development and differentiation during pregnancy. We hypothesize that myoepithelial cells, through elaboration of the ECM and via integrin-based signaling cascades regulate mammary development and differentiation. We have produced a transgenic animal model in which a K5 promoter directs expression of the E2F-1 transgene to mammary myoepithelial cells. Our characterization of whole mounts revealed that glands from virgin transgenics had profoundly reduced ductal arborization and branching compared to those from wild types. Proliferation was decreased and apoptosis increased in the transgenic glands, compared to wild types. Alveolar development was severely curtailed in glands harvested from pregnant transgenics, and numbers of myoepithelial cells in the mammaries were reduced. Taken together, these data suggest that E2F-1 over expression induces apoptosis of myoepithelial cells, and this loss of myoepithelial control affects ductal development and inhibits the acquisition of the differentiated phenotype of pregnancy. Since the structural and functional differentiation achieved during gestation is protective against breast cancer, the myoepithelial cells can be considered mediators of the susceptibility of the glands to tumorigenesis and novel targets for preventive and therapeutic strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA388224
Entities
People
- Robin S. Fuchs-young
Organizations
- The University of Texas MD Anderson Cancer Center