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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-4-23
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pubmed:abstractText |
In lung adenocarcinoma, expression of Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) is a predictor of survival while that of interleukin (IL)-8 is associated with a poor prognosis. In several models, tumorigenesis is abolished by RANTES, while it is facilitated by IL-8. We studied the regulation of RANTES and IL-8 expression in A549 lung adenocarcinoma cells. The effects of tumor necrosis factor (TNF)-alpha and regulators of protein kinases C (PKC)alpha/beta were tested because these have been shown to modulate cancer development and progression. TNF-alpha stimulated expression of both chemokines, while the PKCalpha/beta activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced only expression of IL-8 and inhibited TNF-alpha-induced RANTES expression. The PKCalpha/beta inhibitor Gö 6976 increased TNF-alpha-induced RANTES production and prevented its down-regulation by TPA. In contrast, it decreased TNF-alpha or TPA-induced IL-8 release. The differential regulation of RANTES and IL-8 expression was further analyzed. Site-directed mutagenesis indicated that regulation of RANTES promoter activity required two nuclear factor (NF)-kappaB response elements but not its activator protein (AP)-1 binding sites. An AP-1 and a NF-kappaB recognition sites were necessary for full induction of IL-8 promoter activity by TNF-alpha and TPA. Moreover, electrophoretic mobility shift assays demonstrated that NF-kappaB response elements from the RANTES promoter were of lower affinity than that from the IL-8 promoter. Immunoblotting experiments showed that TPA was more potent than TNF-alpha to induce in a PKCalpha/beta dependent manner the p44/p42 mitogen-activated protein kinases (MAPK) signaling cascade which controls AP-1 activity. Conversely, TPA inhibited TNF-alpha-induced NF-kappaB signaling and was a weak activator of this pathway. Thus, TPA did not sufficiently activate NF-kappaB to increase transcription through the low affinity NF-kappaB binding sites on RANTES promoter and its inhibitory effect on TNF-alpha-induced NF-kappaB signaling resulted in a reduced transcription rate. On IL-8 promoter, increased transcription through the high affinity NF-kappaB binding site occurred even with poorly activated NF-kappaB and the functional AP-1 response element compensated any loss of transcription rate. These data provide a mechanistic insight into the differential regulation of IL-8 and RANTES expression by PKCalpha/beta in lung adenocarcinoma cells.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10329603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10330400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10435109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10493525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10679119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-10786697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-11069840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-11234881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-11294822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-11733537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-12107097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-12171898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-12213593,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-14597737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-14678997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-14687724,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-15208657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-15229479,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-2557547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-8433394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-8462247,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-8464749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-8675690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-8864755,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-9120310,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17207890-9885227
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0169-5002
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
167-74
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17207890-Adenocarcinoma,
pubmed-meshheading:17207890-Blotting, Northern,
pubmed-meshheading:17207890-Blotting, Western,
pubmed-meshheading:17207890-Carcinogens,
pubmed-meshheading:17207890-Cell Line, Tumor,
pubmed-meshheading:17207890-Chemokine CCL5,
pubmed-meshheading:17207890-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:17207890-Humans,
pubmed-meshheading:17207890-Interleukin-8,
pubmed-meshheading:17207890-Lung Neoplasms,
pubmed-meshheading:17207890-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17207890-NF-kappa B,
pubmed-meshheading:17207890-Promoter Regions, Genetic,
pubmed-meshheading:17207890-Protein Kinase C,
pubmed-meshheading:17207890-Signal Transduction,
pubmed-meshheading:17207890-Tetradecanoylphorbol Acetate,
pubmed-meshheading:17207890-Transcription Factor AP-1,
pubmed-meshheading:17207890-Transfection,
pubmed-meshheading:17207890-Tumor Necrosis Factor-alpha
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pubmed:year |
2007
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pubmed:articleTitle |
Differential regulation of RANTES and IL-8 expression in lung adenocarcinoma cells.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale U454-IFR3, 34295 Montpellier cedex 5, France.
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pubmed:publicationType |
Journal Article
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