Interleukin-8 confers androgen-independent growth and migration of LNCaP: Differential effects of tyrosine kinases Src and FAK

Li Fen Lee, Maggie C. Louie, Sonal J. Desai, Joy Yang, Hongwu Chen, Christopher P Evans, Hsing-Jien Kung

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

Interleukin-8 (IL-8), a chemokine implicated in the metastasis and angiogenesis of a variety of cancers, has been reported to be overexpressed in prostate cancer. In this study, we ascribe a new role for IL-8 in prostate cancer progression using LNCaP cells. We demonstrate that IL-8 activates the androgen receptor and confers androgen-independent growth, while serving as a potent chemotactic factor. Our evaluation of the possible signal pathways involved in androgen-independence and cell migration shows that the tyrosine kinases Src and FAK (focal adhesion kinase) are involved in IL-8-induced signaling. Pharmacological and genetic inhibitors of Src and FAK interfere with IL-8-induced cell migration, while only the Src inhibitor was able to repress androgen-independent growth. This suggests that both growth and migration depend on the activity of Src, whereas cell migration also requires the activation of FAK. Our evidence that IL-8-induced androgen-independent growth is, at least in part, due to androgen receptor activation includes (1) an inhibitor of androgen receptor activity diminishes cell growth; (2) androgen receptor transactivation potential is augmented by IL-8 and (3) androgen receptor is recruited to the promoter of prostate specific antigen (PSA) upon IL-8 treatment, based on chromatin immunoprecipitation experiments. Taken together, our data suggest that in addition to its role in metastasis and angiogenesis, IL-8 may also serve as a facilitator for androgen-independent transition of prostate cancers. To our knowledge, this is the first report about the tyrosine kinase signals and androgen receptor activation induced by IL-8 in prostate cancer cells. The observation that IL-8 mediates its growth and chemotactic effects via Src and FAK suggests the potential use for tyrosine kinase inhibitors at early stage of prostate cancer development.

Original languageEnglish (US)
Pages (from-to)2197-2205
Number of pages9
JournalOncogene
Volume23
Issue number12
DOIs
StatePublished - Mar 18 2004

Keywords

  • Androgen-independence
  • Focal adhesion kinase
  • Interleukin-B
  • LNCAP
  • Migration
  • Src

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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