Linked Life Data

16778189

Source:http://linkedlifedata.com/resource/pubmed/id/16778189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-6-16
pubmed:abstractText
The development and progression of malignancies is a complex multistage process that involves the contribution of a number of genes giving growth advantage to cells when transformed. The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex with tumor-suppressor or prooncogenic activities depending on the cell type and the stage of the disease. We have previously reported the identification of a novel WD-domain protein, STRAP, that associates with both TGF-beta receptors and that synergizes with the inhibitory Smad, Smad7, in the negative regulation of TGF-beta-induced transcription. Here, we show that STRAP is ubiquitously expressed and is localized in both cytoplasm and nucleus. STRAP is up-regulated in 60% colon and in 78% lung carcinomas. Stable expression of STRAP results in activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and in down-regulation of the cyclin-dependent kinase inhibitor p21(Cip1), which results in retinoblastoma protein hyperphosphorylation. In addition, we have observed that Smad2/3 phosphorylation, TGF-beta-mediated transcription, and growth inhibition are induced in STRAP-knockout mouse embryonic fibroblasts compared with wild-type cells. Ectopic expression of STRAP in A549 lung adenocarcinoma cell line inhibits TGF-beta-induced growth inhibition and enhances anchorage-independent growth of these cells. Moreover, overexpression of STRAP increases tumorigenicity in athymic nude mice. Knockdown of endogenous STRAP by small interfering RNA increases TGF-beta signaling, reduces ERK activity, increases p21(Cip1) expression, and decreases tumorigenicity. Taken together, these results suggest that up-regulation of STRAP in human cancers may provide growth advantage to tumor cells via TGF-beta-dependent and TGF-beta-independent mechanisms, thus demonstrating the oncogenic function of STRAP.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6156-66
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16778189-Animals, pubmed-meshheading:16778189-COS Cells, pubmed-meshheading:16778189-Cell Transformation, Neoplastic, pubmed-meshheading:16778189-Cercopithecus aethiops, pubmed-meshheading:16778189-Colorectal Neoplasms, pubmed-meshheading:16778189-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:16778189-Enzyme Activation, pubmed-meshheading:16778189-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16778189-Humans, pubmed-meshheading:16778189-Lung Neoplasms, pubmed-meshheading:16778189-MAP Kinase Signaling System, pubmed-meshheading:16778189-Mice, pubmed-meshheading:16778189-Mink, pubmed-meshheading:16778189-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:16778189-NIH 3T3 Cells, pubmed-meshheading:16778189-Neoplasm Proteins, pubmed-meshheading:16778189-Oncogenes, pubmed-meshheading:16778189-Phosphorylation, pubmed-meshheading:16778189-Proteins, pubmed-meshheading:16778189-Retinoblastoma Protein, pubmed-meshheading:16778189-Transforming Growth Factor beta
pubmed:year
2006
pubmed:articleTitle
Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis.
pubmed:affiliation
Department of Surgery, Vanderbilt-Ingram Cancer Center, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural