Abstract
Microdissection and differential display PCR were used to identify genes preferentially expressed in the highly proliferative terminal end buds (TEBs) in the mammary gland of 45-day-old virgin rats. One clone exhibited 87% homology to the human p190-B gene encoding a novel Rho-Gap. Using in situ hybridization, p190-B was detected in both the TEBs and the terminal ducts, with the highest expression observed in the outer layer of TEBs. During normal mammary gland development, p190-B mRNA expression was highest in the virgin mammary gland and decreased during late pregnancy and lactation. Interestingly, increased levels of p190-B mRNA relative to the normal mammary gland were seen in a subset of murine mammary tumors that appeared to be less well differentiated and potentially more aggressive. Transient transfection of a p190-B expression construct into MCF-10A human mammary epithelial cells resulted in disruption of the actin cytoskeleton, which suggests a role for p190-B in regulating the signaling pathways that influence cell migration and invasion. These results suggest that p190-B may be required for virgin mammary gland development, and its aberrant expression may occur in breast cancer.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Biomarkers
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Breast / metabolism*
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Cell Line
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Coloring Agents
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Cytoskeleton / metabolism
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DNA, Complementary
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DNA-Binding Proteins
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Epithelial Cells / metabolism
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Female
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GTPase-Activating Proteins
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Gene Expression Profiling
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Guanine Nucleotide Exchange Factors*
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Humans
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In Situ Hybridization
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Mammary Glands, Animal / anatomy & histology
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Mammary Glands, Animal / growth & development*
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Mammary Glands, Animal / metabolism*
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / metabolism*
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Mammary Neoplasms, Experimental / pathology
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Mice
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Microscopy, Fluorescence
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Pregnancy
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RNA / metabolism
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Rats
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Rats, Inbred WF
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Recombinant Proteins / metabolism
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Repressor Proteins
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Transfection
Substances
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ARHGAP35 protein, human
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ARHGAP5 protein, human
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Actins
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Arhgap35 protein, mouse
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Arhgap35 protein, rat
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Arhgap5 protein, mouse
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Biomarkers
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Coloring Agents
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DNA, Complementary
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DNA-Binding Proteins
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GTPase-Activating Proteins
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Guanine Nucleotide Exchange Factors
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Nuclear Proteins
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Phosphoproteins
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Recombinant Proteins
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Repressor Proteins
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RNA