title: Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Urology and Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Lou
authors.forename: Min
authors.initials: M
authors.lastname: Hou
authors.forename: Fernando
authors.initials: F
authors.lastname: de Miguel
authors.forename: Lizabeth
authors.initials: L
authors.lastname: Gerber
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
mesh_terms: 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
chemical_list: 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