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

Soo Ok Lee, Wei Lou, Min Hou, Fernando De Miguel, Lizabeth Gerber, Allen C Gao

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157 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)370-376
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number1 I
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Lee, S. O., Lou, W., Hou, M., De Miguel, F., Gerber, L., & Gao, A. C. (2003). Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells. Clinical Cancer Research, 9(1 I), 370-376.