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

Oncogene. 2004 Mar 18;23(12):2197-205. doi: 10.1038/sj.onc.1207344.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgens / metabolism*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Chemotaxis / drug effects
  • Chromatin / metabolism
  • Enzyme Activation
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Interleukin-8 / metabolism*
  • Interleukin-8 / pharmacology
  • Male
  • Precipitin Tests
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Time Factors
  • Trans-Activators / metabolism
  • Transcriptional Activation
  • src-Family Kinases / metabolism*


  • Androgens
  • Chromatin
  • Interleukin-8
  • Receptors, Androgen
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • src-Family Kinases
  • Prostate-Specific Antigen