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, Hong Wu Chen, Christopher P. Evans, Hsing Jien Kung

Research output: Contribution to journalArticle

158 Citations (Scopus)

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
Pages (from-to)2197-2205
Number of pages9
JournalOncogene
Volume23
Issue number12
DOIs
Publication statusPublished - Mar 18 2004
Externally publishedYes

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
src-Family Kinases
Interleukin-8
Androgens
Androgen Receptors
Growth
Prostatic Neoplasms
Cell Movement
Neoplasm Metastasis
Chromatin Immunoprecipitation
Interleukin-3
Chemotactic Factors
Receptor Protein-Tyrosine Kinases
Prostate-Specific Antigen
Chemokines
Protein-Tyrosine Kinases
Transcriptional Activation
Signal Transduction
Pharmacology

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Interleukin-8 confers androgen-independent growth and migration of LNCaP : Differential effects of tyrosine kinases Src and FAK. / Lee, Li Fen; Louie, Maggie C.; Desai, Sonal J.; Yang, Joy; Chen, Hong Wu; Evans, Christopher P.; Kung, Hsing Jien.

In: Oncogene, Vol. 23, No. 12, 18.03.2004, p. 2197-2205.

Research output: Contribution to journalArticle

Lee, Li Fen ; Louie, Maggie C. ; Desai, Sonal J. ; Yang, Joy ; Chen, Hong Wu ; Evans, Christopher P. ; Kung, Hsing Jien. / Interleukin-8 confers androgen-independent growth and migration of LNCaP : Differential effects of tyrosine kinases Src and FAK. In: Oncogene. 2004 ; Vol. 23, No. 12. pp. 2197-2205.
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AU - Evans, Christopher P.

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AB - 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.

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