Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells.
Interleukin 6 (IL-6) plays important roles in the immune system, hematopoiesis, as well as the growth of various tumors. Androgens are important in the initiation and progression of prostate cancer and their effects are mediated by androgen receptor (AR). Here we present a molecular mechanism for the effects of IL-6 on prostate cancer cells through a cross-talk between IL-6 and AR signaling pathways. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT). In addition, DHT treatment augmented endogenous STAT3-mediated gene expression by IL-6. Conversely, DHT-induced AR activity was increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation. In contrast, DHT-mediated enhancement of STAT3 activation was inhibited by flutamide, an AR antagonist. We provide evidence that these activities are due to direct physical interactions between STAT3 and AR in prostate cancer cells.
Matsuda
T
T
Department of Immunology, Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan. tmatsuda@ms.toyama-mpu.ac.jp
Junicho
A
A
Yamamoto
T
T
Kishi
H
H
Korkmaz
K
K
Saatcioglu
F
F
Fuse
H
H
Muraguchi
A
A
D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004357:Drug Synergism; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011944:Receptors, Androgen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D013196:Dihydrotestosterone; D005485:Flutamide