Oncostatin M (OM) promotes the growth of DU 145 human prostate cancer cells, but not PC-3 or LNCaP, through the signaling of the OM specific receptor.
BACKGROUND
Oncostain M (OM) is a member of the interleukin-6 (IL-6) cytokine family and all members utilize gp130 as a common signal transducing receptor. Tyrosine phosphorylation of the transcription factor STAT3 plays an important role in IL-6 cytokine family-mediated reactions. OM signals are transduced through two different OM receptor complexes: a leukemia inhibitory factor (LIF)/OM receptor (a heterodimer of LIFR beta and gp130) and an OM specific receptor (a heterodimer of OMR beta and gp130). This study examined the expression of these two OM receptors as well as the effect of OM on the growth of prostate carcinoma cell lines.


METHODS
PC-3, DU 145 and LNCaP cells were used. The expression of OMR beta and LIFR beta was determined by RT-PCR. Tyrosine phosphorylation of STAT3 was analyzed by Western blotting.


RESULTS
OM promoted the growth of DU 145 but not that of PC-3 and LNCaP. LIF had no effect on the growth of any of these cell lines. DU 145 and PC-3 expressed much higher levels of OMR beta mRNA than those of LIFR beta mRNA. Neither OMR beta nor LIFR beta mRNA was detected in LNCaP. OM, but not LIF, induced rapid tyrosine phosphorylation of STAT3 in DU 145. PC-3 lacked STAT3 expression.


CONCLUSIONS
OM has been known to be a cytostatic cytokine for tumor cells. Conversely, we show that OM promotes the growth of DU 145. Further, our findings suggest that the growth-promoting signals of OM is mediated through the OM specific receptor with subsequent activation of STAT3.
Mori
S
S
Department of Microbiology and Immunology, UCLA School of Medicine 90095-1747, USA.
Murakami-Mori
K
K
Bonavida
B
B
D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D018121:Receptors, Cytokine / Q000502:physiology*; D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000502:physiology
D016207:Cytokines; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D053683:Oncostatin M