Source:http://linkedlifedata.com/resource/pubmed/id/16648560
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2006-5-1
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| pubmed:abstractText |
Advanced and hormone-refractory prostate cancer has long been considered as a chemoresistant disease. Recently, it was found that 14-3-3sigma expression increases as prostate tumor progresses, and that 14-3-3sigma contributes significantly to drug resistance in breast cancers. We, thus, hypothesized that advanced and hormone-refractory prostate cancers may have an increased level of 14-3-3sigma, which in turn may contribute to drug resistance in advanced and hormone-refractory prostate cancers. In this study, we tested this hypothesis and found that, indeed, the expression level of 14-3-3sigma in androgen-independent prostate cancer cell lines DU145, PC3, and CWR22RV are much higher than that in the androgen-dependent cell line LNCaP, and that the androgen-independent cells are more resistant to mitoxantrone and Adriamycin than the androgen-dependent cells. Depleting 14-3-3sigma expression in DU145 and CWR22RV by RNA interference significantly sensitized these cells to mitoxantrone and Adriamycin by abrogating G2-M checkpoint and increasing apoptosis, whereas restoring 14-3-3sigma expression in LNCaP cells enhanced drug resistance. We also showed that 14-3-3sigma deficiency caused nuclear localization of Cdc2 and dephosphorylation of the Tyr15 residue upon DNA damage. Based on these studies, we propose that therapeutic intervention targeting 14-3-3sigma may be useful for sensitizing hormone-refractory prostate cancers to chemotherapy by both G2-M checkpoint abrogation and apoptosis enhancement.
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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/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Exonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitoxantrone,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/SFN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1535-7163
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
5
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
903-12
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:16648560-14-3-3 Proteins,
pubmed-meshheading:16648560-Apoptosis,
pubmed-meshheading:16648560-Base Sequence,
pubmed-meshheading:16648560-Cell Cycle,
pubmed-meshheading:16648560-Cell Line,
pubmed-meshheading:16648560-Cell Line, Tumor,
pubmed-meshheading:16648560-Epithelial Cells,
pubmed-meshheading:16648560-Exonucleases,
pubmed-meshheading:16648560-Humans,
pubmed-meshheading:16648560-Male,
pubmed-meshheading:16648560-Mitoxantrone,
pubmed-meshheading:16648560-Molecular Sequence Data,
pubmed-meshheading:16648560-Neoplasm Proteins,
pubmed-meshheading:16648560-Prostate,
pubmed-meshheading:16648560-Prostatic Neoplasms,
pubmed-meshheading:16648560-RNA, Small Interfering,
pubmed-meshheading:16648560-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16648560-Transfection,
pubmed-meshheading:16648560-Tumor Markers, Biological
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| pubmed:year |
2006
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| pubmed:articleTitle |
Sensitizing hormone-refractory prostate cancer cells to drug treatment by targeting 14-3-3sigma.
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| pubmed:affiliation |
Department of Pharmacology and Toxicology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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