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


METHODS
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.
Lee
Soo Ok
SO
Department of Urology and Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Lou
Wei
W
Hou
Min
M
de Miguel
Fernando
F
Gerber
Lizabeth
L
Gao
Allen C
AC
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004396:Coloring Agents; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators; C022616:thiazolyl blue