Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells.
The effects of IL-6 on prostate cancer cells are well documented yet remain controversial. Some reports suggested that IL-6 could promote prostate cancer cell growth, while others showed that IL-6 could repress prostate cancer cell growth. Here, we systemically examined various IL-6 signaling pathways in prostate cancer cells and found that IL-6 could go through at least three distinct pathways to modulate the functions of androgen receptor (AR), a key transcriptional factor to control the prostate cancer growth. Our results show that IL-6 can enhance AR transactivation via either the STAT3 or MAPK pathways. In contrast, IL-6 can suppress AR transactivation via the PI3K-Akt pathway. Co-existence of these various signaling pathways may result in either additive or conflicting effects on AR transactivation. Together, our results indicate that the balance of these various pathways may then determine the overall effect of IL-6 on AR transactivation.
Yang
Lin
L
George Whipple Lab for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Wang
Liang
L
Lin
Hui-Kuan
HK
Kan
Pu-Yeh
PY
Xie
Shaozhen
S
Tsai
Meng-Yin
MY
Wang
Peng-Hui
PH
Chen
Yen-Ta
YT
Chang
Chawnshang
C
D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C494086:STAT3 protein, human; C494918:AKT1 protein, human