Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways.
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.
Mesh Terms:
Amino Acids, Anilides, Blotting, Northern, DNA-Binding Proteins, Dose-Response Relationship, Drug, Enzyme Activation, Forskolin, Humans, Immunoblotting, Interleukin-6, Janus Kinase 1, Luciferases, MAP Kinase Signaling System, Male, Models, Biological, Nitriles, Phosphorylation, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Prostatic Neoplasms, Protein Binding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Signal Transduction, Tetrazolium Salts, Thiazoles, Tosyl Compounds, Trans-Activators, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Amino Acids, Anilides, Blotting, Northern, DNA-Binding Proteins, Dose-Response Relationship, Drug, Enzyme Activation, Forskolin, Humans, Immunoblotting, Interleukin-6, Janus Kinase 1, Luciferases, MAP Kinase Signaling System, Male, Models, Biological, Nitriles, Phosphorylation, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Prostatic Neoplasms, Protein Binding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Signal Transduction, Tetrazolium Salts, Thiazoles, Tosyl Compounds, Trans-Activators, Transcriptional Activation, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: Mar. 01, 2002
PubMed ID: 11751884
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