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Clin Cancer Res. 2003 Jan;9(1):370-6.

Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells.

Author information

1
Department of Urology and Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.

Abstract

PURPOSE:

Prostate cancer frequently progresses from an initial androgen dependence to androgen independence, rendering the only effective androgen ablation therapy useless. The mechanism underlying the androgen-independent progression is incompletely understood. Interleukin (IL)-6 has been implicated in this androgen-independent progression. In this study, we tested whether IL-6 induces androgen-independent growth both in vitro and in vivo.

EXPERIMENTAL DESIGN:

IL-6 was expressed in androgen-sensitive LNCaP cells. The effects of IL-6 on androgen receptor activity was determined by Northern blots and gel shift assays. The effects of IL-6 on LNCaP cell growth were determined in vitro by MTT assay and in vivo.

RESULTS:

IL-6 can enhance the growth of androgen-sensitive LNCaP cells in the androgen-deprived condition in vitro, which is accompanied by elevation of androgen-regulated prostate-specific antigen mRNA expression. IL-6 promotes androgen-sensitive LNCaP cell tumor growth in the castrated male mice. IL-6 enhances androgen receptor DNA binding activity and nuclear translocation. The androgen-independent phenotype induced by IL-6 in LNCaP cells is accompanied by significant activation of signal transducers and activators of transcription 3 and mitogen-activated protein kinase signal pathways.

CONCLUSIONS:

These studies clearly provide experimental evidence that IL-6 initiates and/or enhances the transition of prostate cancer cells from an androgen-dependent to an androgen-independent phenotype.

PMID:
12538490
[Indexed for MEDLINE]
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