Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-25
pubmed:abstractText
p190-B Rho GTPase activating protein is essential for mammary gland development because p190-B deficiency prevents ductal morphogenesis. To investigate the role of p190-B during distinct stages of mammary gland development, tetracycline-regulatable p190-B-overexpressing mice were generated. Short-term induction of p190-B in the developing mammary gland results in abnormal terminal end buds (TEBs) that exhibit aberrant budding off the neck, histological anomalies, and a markedly thickened stroma. Overexpression of p190-B throughout postnatal development results in increased branching, delayed ductal elongation, and disorganization of the ductal tree. Interestingly, overexpression of p190-B during pregnancy results in hyperplastic lesions. Several cellular and molecular alterations detected within the aberrant TEBs may contribute to these phenotypes. Signaling through the IGF pathway is altered, and the myoepithelial cell layer is discontinuous at sites of aberrant budding. An increase in collagen and extensive infiltration of macrophages, which have recently been implicated in branching morphogenesis, is observed in the stroma surrounding the p190-B-overexpressing TEBs. We propose that the stromal response, disruption of the myoepithelial layer, and alterations in IGF signaling in the p190-B-overexpressing mice impact the TEB architecture, leading to disorganization and increased branching of the ductal tree. Moreover, we suggest that alterations in tissue architecture and the adjacent stroma as a consequence of p190-B overexpression during pregnancy leads to loss of growth control and the formation of hyperplasia. These data demonstrate that precise control of p190-B Rho GTPase-activating protein activity is critical for normal branching morphogenesis during mammary gland development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ARHGAP35 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ARHGAP5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Arhgap5 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Grlf1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1391-405
pubmed:dateRevised
2011-9-27
pubmed:meshHeading
pubmed-meshheading:16469769-Animals, pubmed-meshheading:16469769-Base Sequence, pubmed-meshheading:16469769-Carrier Proteins, pubmed-meshheading:16469769-DNA, Complementary, pubmed-meshheading:16469769-DNA-Binding Proteins, pubmed-meshheading:16469769-Female, pubmed-meshheading:16469769-GTPase-Activating Proteins, pubmed-meshheading:16469769-Gene Expression, pubmed-meshheading:16469769-Guanine Nucleotide Exchange Factors, pubmed-meshheading:16469769-Humans, pubmed-meshheading:16469769-Hyperplasia, pubmed-meshheading:16469769-Mammary Glands, Animal, pubmed-meshheading:16469769-Mice, pubmed-meshheading:16469769-Mice, Inbred Strains, pubmed-meshheading:16469769-Mice, Transgenic, pubmed-meshheading:16469769-Phenotype, pubmed-meshheading:16469769-Pregnancy, pubmed-meshheading:16469769-Recombinant Proteins, pubmed-meshheading:16469769-Repressor Proteins, pubmed-meshheading:16469769-Signal Transduction
pubmed:year
2006
pubmed:articleTitle
P190-B Rho GTPase-activating protein overexpression disrupts ductal morphogenesis and induces hyperplastic lesions in the developing mammary gland.
pubmed:affiliation
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural