Source:http://linkedlifedata.com/resource/pubmed/id/15922743
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2005-5-30
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| pubmed:abstractText |
Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0014-4827
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
307
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
231-46
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15922743-Animals,
pubmed-meshheading:15922743-Apoptosis,
pubmed-meshheading:15922743-Blotting, Western,
pubmed-meshheading:15922743-COS Cells,
pubmed-meshheading:15922743-Cell Line,
pubmed-meshheading:15922743-Cercopithecus aethiops,
pubmed-meshheading:15922743-DNA-Binding Proteins,
pubmed-meshheading:15922743-Dose-Response Relationship, Drug,
pubmed-meshheading:15922743-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15922743-Growth Inhibitors,
pubmed-meshheading:15922743-Humans,
pubmed-meshheading:15922743-Mice,
pubmed-meshheading:15922743-Mice, Nude,
pubmed-meshheading:15922743-Neoplasm Transplantation,
pubmed-meshheading:15922743-Neoplasms,
pubmed-meshheading:15922743-Precipitin Tests,
pubmed-meshheading:15922743-Retroviridae,
pubmed-meshheading:15922743-Signal Transduction,
pubmed-meshheading:15922743-Smad7 Protein,
pubmed-meshheading:15922743-Trans-Activators,
pubmed-meshheading:15922743-Transcription, Genetic,
pubmed-meshheading:15922743-Transfection,
pubmed-meshheading:15922743-Transforming Growth Factor beta,
pubmed-meshheading:15922743-Transplantation, Heterologous
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| pubmed:year |
2005
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| pubmed:articleTitle |
Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.
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| pubmed:affiliation |
Department of Surgery, Vanderbilt University School of Medicine, 1161 21st Avenue South, D5230 MCN, Nashville, TN 37232, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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