18316594

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0600210, umls-concept:C1269955, umls-concept:C1336624, umls-concept:C1512505, umls-concept:C1879547, umls-concept:C2349975, umls-concept:C2699153
pubmed:issue	5
pubmed:dateCreated	2008-3-4
pubmed:abstractText	TGFBR16A is a common hypomorphic variant of the type 1 transforming growth factor beta receptor (TGFBR1), which has been associated with increased cancer risk in some studies. Although TGFBR16A is capable of switching TGF-beta growth-inhibitory signals into growth-stimulatory signals when stably transfected into MCF-7 breast cancer cells, the biological effects of TGFBR16A are largely unknown. To broadly explore the potential oncogenic properties of TGFBR16A, we assessed its effects on NIH-3T3 cells as well as its effect on the migration and invasion of MCF-7 cells. We found that TGFBR16A has decreased oncogenic properties compared with TGFBR1. However, TGFBR16A significantly enhances MCF-7 cell migration and invasion in a TGF-beta signaling-independent manner. Gene expression profiling studies identified two down-regulated genes involved in cell migration and invasion: ARHGAP5, encoding ARHGAP5, and FN1, encoding fibronectin-1 (FN1). ARHGAP5 and FN1 expression was similarly down-regulated in MCF-7 cells stably transfected with a kinase-inactivated TGFBR16A construct. Functional assays show that TGFBR16A-mediated decreased ARHGAP5 expression is associated with higher RhoA activation, a crucial mediator of cell migration. Extracellular signal-regulated kinase (ERK) activation is also higher in cells that harbor the TGFBR16A allele. We conclude that TGFBR16A is not an oncogene but enhances MCF-7 cell migration and invasion through RhoA and ERK pathway activation and down-regulates two crucial mediators of this phenotype. These results provide the first evidence that TGFBR1*6A may contribute to cancer progression in a TGF-beta signaling-independent manner.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/CA108741, http://linkedlifedata.com/resource/pubmed/grant/CA112520, http://linkedlifedata.com/resource/pubmed/grant/P60 AR048098-060007, http://linkedlifedata.com/resource/pubmed/grant/P60 AR048098-070007, http://linkedlifedata.com/resource/pubmed/grant/R01 CA108741-01A2, http://linkedlifedata.com/resource/pubmed/grant/R01 CA112520-01A1, http://linkedlifedata.com/resource/pubmed/grant/R01 CA112520-08
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pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2984705R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP..., http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RHOA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth..., http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor, http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
pubmed:status	MEDLINE
pubmed:month	Mar
pubmed:issn	1538-7445
pubmed:author	pubmed-author:HuangChiang-ChingCC, pubmed-author:PascheBorisB, pubmed-author:PhukanSharbaniS, pubmed-author:RosmanDiana SDS
pubmed:issnType	Electronic
pubmed:day	1
pubmed:volume	68
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	1319-28
pubmed:dateRevised	2011-6-20
pubmed:meshHeading	pubmed-meshheading:18316594-Animals, pubmed-meshheading:18316594-Cell Line, Tumor, pubmed-meshheading:18316594-Cell Movement, pubmed-meshheading:18316594-Cell Proliferation, pubmed-meshheading:18316594-Enzyme Activation, pubmed-meshheading:18316594-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:18316594-Gene Expression Profiling, pubmed-meshheading:18316594-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18316594-Humans, pubmed-meshheading:18316594-Mice, pubmed-meshheading:18316594-NIH 3T3 Cells, pubmed-meshheading:18316594-Neoplasm Invasiveness, pubmed-meshheading:18316594-Protein-Serine-Threonine Kinases, pubmed-meshheading:18316594-Receptors, Transforming Growth Factor beta, pubmed-meshheading:18316594-Signal Transduction, pubmed-meshheading:18316594-rhoA GTP-Binding Protein
pubmed:year	2008
pubmed:articleTitle	TGFBR1*6A enhances the migration and invasion of MCF-7 breast cancer cells through RhoA activation.
pubmed:affiliation	Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 880, Chicago, IL 60611, USA.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural