| Identification of functionally distinct TRAF proinflammatory and phosphatidylinositol 3-kinase/mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (PI3K/MEK) transforming activities emanating from RET/PTC fusion oncoprotein. | |
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MedLine Citation:
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PMID: 22158616 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thyroid carcinomas that harbor RET/PTC oncogenes are well differentiated, relatively benign neoplasms compared with those expressing oncogenic RAS or BRAF mutations despite signaling through shared transforming pathways. A distinction, however, is that RET/PTCs induce immunostimulatory programs, suggesting that, in the case of this tumor type, the additional pro-inflammatory pathway reduces aggressiveness. Here, we demonstrate that pro-inflammatory programs are selectively activated by TRAF2 and TRAF6 association with RET/PTC oncoproteins. Eliminating this mechanism reduces pro-inflammatory cytokine production without decreasing transformation efficiency. Conversely, ablating MEK/ERK or PI3K/AKT signaling eliminates transformation but not pro-inflammatory cytokine secretion. Functional uncoupling of the two pathways demonstrates that intrinsic pro-inflammatory pathways are not required for cellular transformation and suggests a need for further investigation into the role inflammation plays in thyroid tumor progression. |
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Authors:
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Josephine H F Wixted; Jay L Rothstein; Laurence C Eisenlohr |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-09 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-06 Completed Date: 2012-03-25 Revised Date: 2012-05-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 3691-703 Citation Subset: IM |
Affiliation:
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Immunology and Microbial Pathogenesis Program, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Humans Inflammation / genetics, metabolism, pathology MAP Kinase Signaling System* Mice Mitogen-Activated Protein Kinase Kinases / genetics, metabolism NIH 3T3 Cells Oncogene Proteins, Fusion / genetics, metabolism* Phosphatidylinositol 3-Kinases / genetics, metabolism* Protein-Tyrosine Kinases / genetics, metabolism* Rats TNF Receptor-Associated Factor 2 / genetics, metabolism* TNF Receptor-Associated Factor 3 / genetics, metabolism* Thyroid Neoplasms / genetics, metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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F31 NS054444/NS/NINDS NIH HHS; F31NS054444/NS/NINDS NIH HHS; R01AI069192/AI/NIAID NIH HHS; R21A1063065//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Oncogene Proteins, Fusion; 0/TNF Receptor-Associated Factor 2; 0/TNF Receptor-Associated Factor 3; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.112/RET-PTC oncoprotein, rat; EC 2.7.1.112/ret-PTC fusion oncoproteins, human; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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