p190-B, a Rho-GTPase-activating protein, is differentially expressed in terminal end buds and breast cancer

Microdissection and differential display PCR were used to identify genes pr eferentially expressed in the highly proliferative terminal end buds (TEBs) in the mammary gland of 45-day-old virgin rats. One clone exhibited 87% ho mology to the human p190-B gene encoding a novel Rho-Gap, Using in situ hyb ridization, p190-B was detected in both the TEBs and the terminal ducts, wi th the highest expression observed in the outer layer of TEBs, During norma l mammary gland development, p190-B mRNA expression was highest in the virg in mammary gland and decreased during late pregnancy and lactation. Interes tingly, increased levels of p190-B mRNA relative to the normal mammary glan d were seen in a subset of murine mammary tumors that appeared to be less w ell differentiated and potentially more aggressive. Transient transfection of a p190-B expression construct into MCF-10A human mammary epithelial cell s resulted in disruption of the actin cytoskeleton, which suggests a role f or p190-B in regulating the signaling pathways that influence cell migratio n and invasion. These results suggest that p190-B may be required for virgi n mammary gland development, and its aberrant expression may occur in breas t cancer.