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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0033684,
umls-concept:C0040132,
umls-concept:C0205314,
umls-concept:C0243044,
umls-concept:C0442805,
umls-concept:C0543431,
umls-concept:C0679622,
umls-concept:C0694890
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pubmed:issue |
42
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pubmed:dateCreated |
2004-10-11
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pubmed:abstractText |
RET/PTC1 is a rearranged form of the RET tyrosine kinase commonly seen in papillary thyroid carcinomas. It has been shown that RET/PTC1 decreases expression of the sodium/iodide symporter (NIS), the molecule that mediates radioiodide therapy for thyroid cancer. Using proteomic analysis, we identify hsp90 and its co-chaperone p50cdc37 as novel proteins associated with RET/PTC1. Inhibition of hsp90 function with 17-allylamino-17-demothoxygeldanamycin (17-AAG) reduces RET/PTC1 protein levels. Furthermore, 17-AAG increases radioiodide accumulation in thyroid cells, mediated in part through a protein kinase A-independent mechanism. We show that 17-AAG does not increase the total amount of NIS protein or cell surface NIS localization. Instead, 17-AAG increases radioiodide accumulation by decreasing iodide efflux. Finally, the ability of 17-AAG to increase radioiodide accumulation is not restricted to thyroid cells expressing RET/PTC1. These findings suggest that 17-AAG may be useful as a chemotherapeutic agent, not only to inhibit proliferation but also to increase the efficacy of radioiodide therapy in patients with thyroid cancer.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/17-(allylamino)-17-demethoxygeldanam...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rifabutin,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/patched receptors,
http://linkedlifedata.com/resource/pubmed/chemical/sodium-iodide symporter
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
43990-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15302866-Animals,
pubmed-meshheading:15302866-Benzoquinones,
pubmed-meshheading:15302866-Cell Line,
pubmed-meshheading:15302866-HSP90 Heat-Shock Proteins,
pubmed-meshheading:15302866-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15302866-Iodine Radioisotopes,
pubmed-meshheading:15302866-Lactams, Macrocyclic,
pubmed-meshheading:15302866-Membrane Proteins,
pubmed-meshheading:15302866-Oncogene Proteins,
pubmed-meshheading:15302866-Proteins,
pubmed-meshheading:15302866-Rats,
pubmed-meshheading:15302866-Receptors, Cell Surface,
pubmed-meshheading:15302866-Recombinant Proteins,
pubmed-meshheading:15302866-Rifabutin,
pubmed-meshheading:15302866-Symporters,
pubmed-meshheading:15302866-Thyroid Gland,
pubmed-meshheading:15302866-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Inhibition of heat shock protein 90, a novel RET/PTC1-associated protein, increases radioiodide accumulation in thyroid cells.
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pubmed:affiliation |
Medical Scientist Program, The Ohio State University College of Medicine, Columbus 43210, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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