p190-B, A Novel RhoGAP, In Mammary Gland Development and Breast Cancer Progression
Abstract
We have examined the effects of loss and gain of p190-B RhoGAP function on embryonic and postnatal mammary gland development respectively. Using inducible p190-B overexpressing mice we have shown that p190-B plays an essential role in the developing mammary gland by regulating both mammary epithelial cell behavior and the microenvironment. lnteresbngly overexpression of p190-B during pregnancy results in hyperplastic lesions suggesting that p190-B may affect breast tumorigenesis. P190-B is also required for embryonic mammary gland development because homozygous deletion of p190-B results in smaller buds with diminished mesenchyme. interactions between the p190-B and IGF-IR signaling pathways affect both embryonic and postnatal mammary gland development. Finally using inducible p190-B overexpressing McF-7 human breast cancer cells we have demonstrated a novel role for p190-B as a regulator of mitosis and cytokinesis. Overexpression of pI 90-B leads to failed cytokinesis multinucleation and potentially genomic instability. We propose that this may be one mechanism by which p190-B contributes to breast tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA469243
Entities
People
- Jeffrey M. Rosen
- Tracy Vargo-gogola
Organizations
- Baylor College of Medicine