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

研究成果: 雜誌貢獻文章

160 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)2197-2205
頁數9
期刊Oncogene
23
發行號12
DOIs
出版狀態已發佈 - 三月 18 2004
對外發佈Yes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

指紋 深入研究「Interleukin-8 confers androgen-independent growth and migration of LNCaP: Differential effects of tyrosine kinases Src and FAK」主題。共同形成了獨特的指紋。

  • 引用此