Abstract
The androgen receptor (AR) is a ligand-activated transcription factor that mediates the biological responses of androgens. However, non-androgenic pathways have also been shown to activate the AR. The mechanism of cross-talk between the interleukin-6 (IL-6) and AR signal transduction pathways was investigated in LNCaP human prostate cancer cells. IL-6 induced several androgen-response element-driven reporters that are dependent upon the AR, increased the phosphorylation of mitogen-activated protein kinase (MAPK), and activated the AR N-terminal domain (NTD). Inhibitors to MAPK and JAK decreased the IL-6-induced phosphorylation of MAPK and activation of the AR NTD. Immunoprecipitation and transactivation studies showed a direct interaction between amino acids 234-558 of the AR NTD and STAT3 following IL-6 treatment of LNCaP cells. These results demonstrate that activation of the human AR NTD by IL-6 was mediated through MAPK and STAT3 signal transduction pathways in LNCaP prostate cancer cells.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acids / chemistry
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Anilides / pharmacology
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Blotting, Northern
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Colforsin / pharmacology
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Enzyme Activation
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Humans
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Immunoblotting
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Interleukin-6 / metabolism*
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Janus Kinase 1
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Luciferases / metabolism
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MAP Kinase Signaling System*
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Male
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Models, Biological
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Nitriles
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Phosphorylation
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Plasmids / metabolism
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Precipitin Tests
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Promoter Regions, Genetic
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Prostatic Neoplasms / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / metabolism
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Receptors, Androgen / chemistry*
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Receptors, Androgen / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor
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Signal Transduction
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Tetrazolium Salts / pharmacology
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Thiazoles / pharmacology
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Tosyl Compounds
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Trans-Activators / metabolism*
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
Substances
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Amino Acids
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Anilides
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DNA-Binding Proteins
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Interleukin-6
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Nitriles
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Receptors, Androgen
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STAT3 Transcription Factor
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STAT3 protein, human
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Tetrazolium Salts
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Thiazoles
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Tosyl Compounds
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Trans-Activators
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Colforsin
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bicalutamide
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Luciferases
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Protein-Tyrosine Kinases
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JAK1 protein, human
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Janus Kinase 1
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thiazolyl blue