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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2007-5-3
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pubmed:abstractText |
Levels of the proinflammatory cytokine interleukin-6 (IL-6) are increased in therapy-resistant prostate cancer. IL-6 has been considered a positive growth factor in late-stage prostate cancer cells and a potential target for therapeutic interference. Effects of inhibition of IL-6 on cell survival were studied in LNCaP-IL6+ cells, a model system for advanced prostate cancer, which produce IL-6. We show that the autocrine IL-6 loop is responsible for resistance to apoptosis and increased cellular levels of myeloid cell leukemia-1 (Mcl-1) protein, an antiapoptotic member of the Bcl-2 family. Treatment of cells with a chimeric anti-IL-6 antibody (CNTO 328) led to the induction of apoptosis and downregulation of Mcl-1 protein levels. Specific knockdown of Mcl-1 gene expression by small interfering RNA also yielded an increase in apoptosis of LNCaP-IL-6+ cells. Vice versa, inactivation of IL-6 autocrine loop had no influence on apoptosis levels in the absence of Mcl-1, thus suggesting this molecule as a mediator of the survival action of IL-6. Mcl-1 protein regulation by the endogenous cytokine directly involved the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. Our data support the concept of anti-IL-6 targeted therapy in therapy-resistant prostate cancer.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...,
http://linkedlifedata.com/resource/pubmed/chemical/siltuximab
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:CavarrettaI TIT,
pubmed-author:CuligZZ,
pubmed-author:FuchsDD,
pubmed-author:HobischAA,
pubmed-author:MoserP LPL,
pubmed-author:NemethJ AJA,
pubmed-author:NeuwirtHH,
pubmed-author:RumpoldHH,
pubmed-author:SteinerHH,
pubmed-author:UntergasserGG,
pubmed-author:ZakiM HMH
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2822-32
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pubmed:dateRevised |
2011-7-29
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pubmed:meshHeading |
pubmed-meshheading:17072336-Antibodies, Monoclonal,
pubmed-meshheading:17072336-Apoptosis,
pubmed-meshheading:17072336-Autocrine Communication,
pubmed-meshheading:17072336-Disease Progression,
pubmed-meshheading:17072336-Flavonoids,
pubmed-meshheading:17072336-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17072336-Humans,
pubmed-meshheading:17072336-Interleukin-6,
pubmed-meshheading:17072336-Male,
pubmed-meshheading:17072336-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17072336-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17072336-Neoplasm Proteins,
pubmed-meshheading:17072336-Prostatic Neoplasms,
pubmed-meshheading:17072336-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17072336-RNA, Small Interfering,
pubmed-meshheading:17072336-Tumor Cells, Cultured
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pubmed:year |
2007
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pubmed:articleTitle |
The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.
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pubmed:affiliation |
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
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pubmed:publicationType |
Journal Article,
Comparative Study
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