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rdf:type |
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lifeskim:mentions |
umls-concept:C0013126,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0334227,
umls-concept:C0376358,
umls-concept:C0599896,
umls-concept:C1335191,
umls-concept:C1539477,
umls-concept:C1709385,
umls-concept:C1718423,
umls-concept:C1879547
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pubmed:issue |
19
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pubmed:dateCreated |
2001-10-4
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pubmed:abstractText |
Prostate cancer cells are generally resistant to apoptosis by conventional therapy. During a search for molecules that may overcome prostate cancer cell survival mechanisms, we identified the prostate apoptosis response-4 (Par-4) gene. Par-4 induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway. Neither Fas pathway activation alone nor inhibition of NF-kappaB activity with IkappaB-super repressor was sufficient to induce apoptosis of prostate cancer cells. Coregulation of these two pathways was essential and sufficient for Par-4 to induce apoptosis. On the other hand, prostate cancer cells LNCaP or normal prostatic epithelial cells that were resistant to apoptosis by Par-4 did not show Fas or FasL trafficking. These findings identify a mechanism of apoptosis by Par-4 and suggest that Par-4 may have therapeutic potential.
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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/Androgens,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Fasl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/prostate apoptosis response-4...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7255-63
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11585763-Androgens,
pubmed-meshheading:11585763-Animals,
pubmed-meshheading:11585763-Antigens, CD95,
pubmed-meshheading:11585763-Apoptosis,
pubmed-meshheading:11585763-Apoptosis Regulatory Proteins,
pubmed-meshheading:11585763-Carrier Proteins,
pubmed-meshheading:11585763-Cell Membrane,
pubmed-meshheading:11585763-Fas Ligand Protein,
pubmed-meshheading:11585763-Humans,
pubmed-meshheading:11585763-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11585763-Male,
pubmed-meshheading:11585763-Membrane Glycoproteins,
pubmed-meshheading:11585763-Mice,
pubmed-meshheading:11585763-NF-kappa B,
pubmed-meshheading:11585763-Neoplasms, Hormone-Dependent,
pubmed-meshheading:11585763-PTEN Phosphohydrolase,
pubmed-meshheading:11585763-Phosphoric Monoester Hydrolases,
pubmed-meshheading:11585763-Prostatic Neoplasms,
pubmed-meshheading:11585763-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11585763-Signal Transduction,
pubmed-meshheading:11585763-Transcription, Genetic,
pubmed-meshheading:11585763-Transfection,
pubmed-meshheading:11585763-Tumor Suppressor Protein p53,
pubmed-meshheading:11585763-Tumor Suppressor Proteins,
pubmed-meshheading:11585763-Xenograft Model Antitumor Assays,
pubmed-meshheading:11585763-bcl-X Protein
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pubmed:year |
2001
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pubmed:articleTitle |
Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression.
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pubmed:affiliation |
Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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