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K Malinowska, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
H Neuwirt, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
I Cavarretta, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
J Bektic, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
H Steiner, Department of Urology, Innsbruck Medical University, Innsbruck, Austria
H Dietrich, Laboratory Animal Facilities, Innsbruck Medical University, Innsbruck, Austria
P Moser, Department of Pathology, Innsbruck Medical University, Innsbruck, Austria
D Fuchs, Biocenter, Innsbruck Medical University, Innsbruck, Austria
A Hobisch, Department of Urology, General Hospital Feldkirch, Feldkirch, Austria
Z Culig, Department of Urology, Innsbruck Medical University, Innsbruck, 6020, Austria

Correspondence: Zoran Culig, Email: zoran.culig{at}i-med.ac.at

Abstract

It is hypothesised that ligand-independent activation of the androgen receptor is one of the mechanisms implicated in tumour progression. However, supportive evidence is limited to the effect of HER-2/neu that stimulates prostate cancer progression through activation of the androgen receptor. In the present study, we have asked whether the proinflammatory cytokine interleukin-6, which is known to stimulate androgen receptor activity and expression of its downstream target genes, may also induce growth of androgen-sensitive cells. We have found that interleukin-6 differentially regulates proliferation of LAPC-4 and MDA PCa 2b cells. In MDA PCa 2b cells, growth stimulation by interleukin-6 was reversed by administration of either the non-steroidal anti-androgen bicalutamide or the inhibitor of the mitogen-activated protein kinase pathway PD98059. Neither cell line was found to express endogenous interleukin-6. Interestingly, the treatment of those prostate cancer cells did not increase phosphorylation of STAT3. The effect of interleukin-6 on stimulation of androgen receptor activity in MDA PCa 2b cells was lower than that of androgen, comparable to findings reported by other researchers. However, growth of MDA PCa 2b xenografts in castrated animals treated with interleukin-6 was similar to that in non-castrated animals. In addition, bicalutamide showed an inhibitory effect on interleukin-6-regulated growth in vivo. Taken together, data in the present study demonstrate that interleukin-6 may cause growth of androgen receptor-positive tumours in vitro and in vivo through activation of the androgen receptor.

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