Source:http://linkedlifedata.com/resource/pubmed/id/18202756
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rdf:type | |
lifeskim:mentions |
umls-concept:C0012634,
umls-concept:C0017262,
umls-concept:C0033684,
umls-concept:C0035020,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0208973,
umls-concept:C0600139,
umls-concept:C1414371,
umls-concept:C1517892,
umls-concept:C1522602,
umls-concept:C1565860,
umls-concept:C1704666,
umls-concept:C1705323,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-18
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pubmed:abstractText |
The human ELAV-like protein HuR is involved in the stabilization of the mRNAs of a group of genes implicated in the regulation of cellular growth, angiogenesis and rapid inflammatory response. HuR is a nuclear shuttling protein, translocating bound mRNAs from the nucleus to the cytoplasm. We have previously observed an increased expression of cyclooxygenase-2 (COX-2) in prostate cancer while cell culture studies have shown that HuR stabilizes the mRNA of COX-2. Based on these mechanistic data, we aimed to investigate the role of HuR in prostate cancer by a tissue-based analysis combined with functional evaluation using a cell culture approach. Investigating 104 primary prostate carcinomas by immunohistochemistry, we found HuR expression to be shifted from a nuclear staining in normal prostate glands to a cytoplasmic staining in carcinoma tissue (p<0.0001). Cytoplasmic HuR expression was significantly correlated with COX-2 expression (p=0.005). Loss of nuclear HuR expression was an indicator of earlier PSA-relapse both in univariate (p=0.04) and multivariate survival analysis (p=0.04). HuR inhibition by Leptomycin B reduced the inducibility of COX-2 in PC-3 prostate cancer cells. We found that the subcellular localization of HuR is deregulated in a subset of prostate carcinomas, and that this deregulation is linked to an altered expression of the tumorigenic COX-2 protein as well as to an adverse patient prognosis. Our results point to a potential prognostic role of HuR expression in prostate cancer diagnostics and propose HuR as a future therapeutic target in prostate cancer therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/ELAVL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/leptomycin B
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1019-6439
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pubmed:author |
pubmed-author:BuckendahlAnn-ChristinAC,
pubmed-author:DenkertCarstenC,
pubmed-author:DietelManfredM,
pubmed-author:JungKlausK,
pubmed-author:KristiansenGlenG,
pubmed-author:NiesporekSilviaS,
pubmed-author:NoskeAureliaA,
pubmed-author:StephanCarstenC,
pubmed-author:ThomaAndreaA,
pubmed-author:WeichertWilkoW
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pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
341-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18202756-Aged,
pubmed-meshheading:18202756-Antigens, Surface,
pubmed-meshheading:18202756-Carcinoma,
pubmed-meshheading:18202756-Cyclooxygenase 2,
pubmed-meshheading:18202756-Disease Progression,
pubmed-meshheading:18202756-Fatty Acids, Unsaturated,
pubmed-meshheading:18202756-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:18202756-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18202756-Humans,
pubmed-meshheading:18202756-Male,
pubmed-meshheading:18202756-Middle Aged,
pubmed-meshheading:18202756-Multivariate Analysis,
pubmed-meshheading:18202756-Prostatic Neoplasms,
pubmed-meshheading:18202756-RNA-Binding Proteins,
pubmed-meshheading:18202756-Recurrence,
pubmed-meshheading:18202756-Treatment Outcome
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pubmed:year |
2008
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pubmed:articleTitle |
Expression of the ELAV-like protein HuR in human prostate carcinoma is an indicator of disease relapse and linked to COX-2 expression.
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pubmed:affiliation |
Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, Berlin, Germany. silvia.niesporek@charite.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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