P190-B, a Novel RhoGAP, in Mammary Gland Development and Breast Cancer Progression
Abstract
We have developed a tetracycline-regulatable p190-B RhoGAP overexpressing mouse model to investigate the role of p190-B in mammary gland development and breast cancer progression. We have now shown that overexpression of p190-B in the developing mammary gland disrupts terminal end bud (TEB) architecture, increases branching, delays ductal elongation, and leads to disorganization of the ductal tree. Several cellular and molecular changes were detected in the p190-B overexpressing TEBs, all of which may contribute to the disruption in ductal morphogenesis. Alterations in the insulin like growth factor (IGF) signaling pathway, pronounced changes in the microenvironment, and discontinuity of the myoepithelial cell layer was detected in the p190-B overexpressing TEBs. Furthermore, overexpression of p190-B during pregnancy results in hyperplastic lesions. This report is the first to demonstrate that overexpression of a RhoGAP in vivo results in neoplastic growth. These results are presented in the manuscript entitled "P190-B overexpression disrupts ductal morphogenesis in the developing in mammary gland," which is attached as Appendix 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA448237
Entities
People
- Jeffrey M. Rosen
- Tracy Vargo-gogola
Organizations
- Baylor College of Medicine