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 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.
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
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Chakravarty
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Roy
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Gonzales
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J
Gay
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Contreras
J M
JM
Rosen
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001940:Breast / Q000378:metabolism*; D002460:Cell Line; D004396:Coloring Agents; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins; D020869:Gene Expression Profiling; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D017403:In Situ Hybridization; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012313:RNA / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014162:Transfection
C074560:ARHGAP35 protein, human; C513043:ARHGAP5 protein, human; D000199:Actins; C513041:Arhgap35 protein, mouse; C513040:Arhgap35 protein, rat; C513042:Arhgap5 protein, mouse; D015415:Biomarkers; D004396:Coloring Agents; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D012313:RNA