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

159 引文 (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

指紋

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

引用此文

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.

於: Oncogene, 卷 23, 編號 12, 18.03.2004, p. 2197-2205.

研究成果: 雜誌貢獻文章

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. 於: Oncogene. 2004 ; 卷 23, 編號 12. 頁 2197-2205.
@article{4b3ee060c4564801a727bd3b2c1b1e37,
title = "Interleukin-8 confers androgen-independent growth and migration of LNCaP: Differential effects of tyrosine kinases Src and FAK",
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.",
keywords = "Androgen-independence, Focal adhesion kinase, Interleukin-B, LNCAP, Migration, Src",
author = "Lee, {Li Fen} and Louie, {Maggie C.} and Desai, {Sonal J.} and Joy Yang and Chen, {Hong Wu} and Evans, {Christopher P.} and Kung, {Hsing Jien}",
year = "2004",
month = "3",
day = "18",
doi = "10.1038/sj.onc.1207344",
language = "English",
volume = "23",
pages = "2197--2205",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Interleukin-8 confers androgen-independent growth and migration of LNCaP

T2 - Differential effects of tyrosine kinases Src and FAK

AU - Lee, Li Fen

AU - Louie, Maggie C.

AU - Desai, Sonal J.

AU - Yang, Joy

AU - Chen, Hong Wu

AU - Evans, Christopher P.

AU - Kung, Hsing Jien

PY - 2004/3/18

Y1 - 2004/3/18

N2 - 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.

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.

KW - Androgen-independence

KW - Focal adhesion kinase

KW - Interleukin-B

KW - LNCAP

KW - Migration

KW - Src

UR - http://www.scopus.com/inward/record.url?scp=1842434391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842434391&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1207344

DO - 10.1038/sj.onc.1207344

M3 - Article

C2 - 14767470

AN - SCOPUS:1842434391

VL - 23

SP - 2197

EP - 2205

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 12

ER -