Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression

Jin Wook Lee, Geun Young Kim, Jae-Hong Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The androgen receptor (AR) plays a central role in the development and progression of prostate cancer. AR expression is maintained throughout the progression of prostate cancer and is also associated with an aggressive, castration-resistant (CR) phenotype. Despite the critical roles of AR expression in prostate cancer progression, the exact signaling mechanism regulating AR expression remains unclear. In this study, we demonstrated that AR expression was increased by a low-affinity leukotriene B4 receptor (BLT2)-linked pathway. We found that BLT2 was overexpressed in AR-positive prostate cancer cells, such as LNCaP cells, and BLT2 inhibition, using an inhibitor or siRNA knockdown, clearly attenuated AR expression and triggered apoptosis in these cells. These results suggest a role for BLT2 in AR expression and the survival of AR-positive prostate cancer cells. Moreover, we found that the NADPH oxidase family protein, Nox4, lay downstream of BLT2 and mediated the production of reactive oxygen species (ROS) and subsequent NF-κB stimulation, thereby inducing AR expression. Taken together, our results demonstrate that BLT2 plays a critical role in AR expression via a Nox4-ROS-NF-κB-linked pathway, thereby mediating the survival of AR-positive prostate cancer cells. Our findings point to BLT2 as a key regulator of AR expression and will contribute to the development of novel therapies for AR-positive prostate cancers, including androgen-responsive and CR prostate cancers.

Original languageEnglish
Pages (from-to)428-433
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number2
DOIs
Publication statusPublished - 2012 Apr 6

Fingerprint

Androgen Receptors
Prostatic Neoplasms
Castration
Cells
Reactive Oxygen Species
Leukotriene B4 Receptors
NADPH Oxidase
Small Interfering RNA
Androgens

Keywords

  • AR
  • BLT2
  • Prostate cancer
  • ROS
  • Survival

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression. / Lee, Jin Wook; Kim, Geun Young; Kim, Jae-Hong.

In: Biochemical and Biophysical Research Communications, Vol. 420, No. 2, 06.04.2012, p. 428-433.

Research output: Contribution to journalArticle

@article{512fefbfc9e741288f36b276cadce3e0,
title = "Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression",
abstract = "The androgen receptor (AR) plays a central role in the development and progression of prostate cancer. AR expression is maintained throughout the progression of prostate cancer and is also associated with an aggressive, castration-resistant (CR) phenotype. Despite the critical roles of AR expression in prostate cancer progression, the exact signaling mechanism regulating AR expression remains unclear. In this study, we demonstrated that AR expression was increased by a low-affinity leukotriene B4 receptor (BLT2)-linked pathway. We found that BLT2 was overexpressed in AR-positive prostate cancer cells, such as LNCaP cells, and BLT2 inhibition, using an inhibitor or siRNA knockdown, clearly attenuated AR expression and triggered apoptosis in these cells. These results suggest a role for BLT2 in AR expression and the survival of AR-positive prostate cancer cells. Moreover, we found that the NADPH oxidase family protein, Nox4, lay downstream of BLT2 and mediated the production of reactive oxygen species (ROS) and subsequent NF-κB stimulation, thereby inducing AR expression. Taken together, our results demonstrate that BLT2 plays a critical role in AR expression via a Nox4-ROS-NF-κB-linked pathway, thereby mediating the survival of AR-positive prostate cancer cells. Our findings point to BLT2 as a key regulator of AR expression and will contribute to the development of novel therapies for AR-positive prostate cancers, including androgen-responsive and CR prostate cancers.",
keywords = "AR, BLT2, Prostate cancer, ROS, Survival",
author = "Lee, {Jin Wook} and Kim, {Geun Young} and Jae-Hong Kim",
year = "2012",
month = "4",
day = "6",
doi = "10.1016/j.bbrc.2012.03.012",
language = "English",
volume = "420",
pages = "428--433",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression

AU - Lee, Jin Wook

AU - Kim, Geun Young

AU - Kim, Jae-Hong

PY - 2012/4/6

Y1 - 2012/4/6

N2 - The androgen receptor (AR) plays a central role in the development and progression of prostate cancer. AR expression is maintained throughout the progression of prostate cancer and is also associated with an aggressive, castration-resistant (CR) phenotype. Despite the critical roles of AR expression in prostate cancer progression, the exact signaling mechanism regulating AR expression remains unclear. In this study, we demonstrated that AR expression was increased by a low-affinity leukotriene B4 receptor (BLT2)-linked pathway. We found that BLT2 was overexpressed in AR-positive prostate cancer cells, such as LNCaP cells, and BLT2 inhibition, using an inhibitor or siRNA knockdown, clearly attenuated AR expression and triggered apoptosis in these cells. These results suggest a role for BLT2 in AR expression and the survival of AR-positive prostate cancer cells. Moreover, we found that the NADPH oxidase family protein, Nox4, lay downstream of BLT2 and mediated the production of reactive oxygen species (ROS) and subsequent NF-κB stimulation, thereby inducing AR expression. Taken together, our results demonstrate that BLT2 plays a critical role in AR expression via a Nox4-ROS-NF-κB-linked pathway, thereby mediating the survival of AR-positive prostate cancer cells. Our findings point to BLT2 as a key regulator of AR expression and will contribute to the development of novel therapies for AR-positive prostate cancers, including androgen-responsive and CR prostate cancers.

AB - The androgen receptor (AR) plays a central role in the development and progression of prostate cancer. AR expression is maintained throughout the progression of prostate cancer and is also associated with an aggressive, castration-resistant (CR) phenotype. Despite the critical roles of AR expression in prostate cancer progression, the exact signaling mechanism regulating AR expression remains unclear. In this study, we demonstrated that AR expression was increased by a low-affinity leukotriene B4 receptor (BLT2)-linked pathway. We found that BLT2 was overexpressed in AR-positive prostate cancer cells, such as LNCaP cells, and BLT2 inhibition, using an inhibitor or siRNA knockdown, clearly attenuated AR expression and triggered apoptosis in these cells. These results suggest a role for BLT2 in AR expression and the survival of AR-positive prostate cancer cells. Moreover, we found that the NADPH oxidase family protein, Nox4, lay downstream of BLT2 and mediated the production of reactive oxygen species (ROS) and subsequent NF-κB stimulation, thereby inducing AR expression. Taken together, our results demonstrate that BLT2 plays a critical role in AR expression via a Nox4-ROS-NF-κB-linked pathway, thereby mediating the survival of AR-positive prostate cancer cells. Our findings point to BLT2 as a key regulator of AR expression and will contribute to the development of novel therapies for AR-positive prostate cancers, including androgen-responsive and CR prostate cancers.

KW - AR

KW - BLT2

KW - Prostate cancer

KW - ROS

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=84862793197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862793197&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2012.03.012

DO - 10.1016/j.bbrc.2012.03.012

M3 - Article

VL - 420

SP - 428

EP - 433

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 2

ER -