IL-6 and PPARgamma signalling in human PC-3 prostate cancer cells.
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and interleukin (IL)-6 are key factors for controlling prostate cancer cell proliferation and survival.


METHODS
Herein we used the natural PPARgamma ligand, 15deoxy Delta12-14 PGJ(2) (15dPGJ(2)), and IL-6 to define their interactions on proliferation and signal transduction in PC-3 cells. Cytotoxic and trypan blue exclusion assays, Western blot analysis of mitogen-activated protein kinases (MAPK) and Janus kinase/Signal transducer and activator of transcription (JAK/Stat) and real-time polymerase chain reaction (PCR) were methods employed as investigation tools.


RESULTS
15dPGJ(2) reduced PC-3 cell proliferation, while IL-6 increased it. IL-6 induced PPARgamma expression but did not affect the PPARgamma ligand-mediated effects on the proliferation of PC-3 cells. However, 15dPGJ(2) inhibited the IL-6-mediated increase of PC-3 cell proliferation. 15dPGJ(2) activated Erk1/2 phosphorylation without affecting Akt phosphorylation and reduced phosphorylated and unphosphorylated Stat3 in PC-3 cells. IL-6 suppressed endogenous activation of Stat3 without affecting Erk1/2 and Akt phosphorylation and suppressed the 15dPGJ(2)-mediated activation of Erk1/2 phosphorylation in PC-3 cells.


CONCLUSIONS
The interplay between PPARgamma ligands and IL-6 signalling could be important in controlling the growth of androgen independent prostate cancer cells as exemplified by PC-3 cells.
Pitulis
Nea
N
Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Goudi 11527, Greece.
Papageorgiou
Efstathia
E
Tenta
Roxane
R
Lembessis
Peter
P
Koutsilieris
Michael
M
D015153:Blotting, Western; D049109:Cell Proliferation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D047495:PPAR gamma; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3