Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer

masaki shiota, ario takeuchi, Akira Yokomizo, Eiji Kashiwagi, Katsunori Tatsugami, Kentaro Kuroiwa, Seiji Naito

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose: There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer. Materials and Methods: We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines. Results: AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance. Conclusions: AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.

Original languageEnglish
Pages (from-to)276-286
Number of pages11
JournalJournal of Urology
Volume188
Issue number1
DOIs
Publication statusPublished - Jul 1 2012

Fingerprint

Androgen Receptors
Urinary Bladder Neoplasms
Doxorubicin
Growth
Androgens
Cell Line
Androgen Antagonists
Messenger RNA
Castration
Real-Time Polymerase Chain Reaction
Cell Survival

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer. / shiota, masaki; takeuchi, ario; Yokomizo, Akira; Kashiwagi, Eiji; Tatsugami, Katsunori; Kuroiwa, Kentaro; Naito, Seiji.

In: Journal of Urology, Vol. 188, No. 1, 01.07.2012, p. 276-286.

Research output: Contribution to journalArticle

@article{3001a7c508204155a5e4dd6b6e589137,
title = "Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer",
abstract = "Purpose: There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer. Materials and Methods: We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines. Results: AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance. Conclusions: AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.",
author = "masaki shiota and ario takeuchi and Akira Yokomizo and Eiji Kashiwagi and Katsunori Tatsugami and Kentaro Kuroiwa and Seiji Naito",
year = "2012",
month = "7",
day = "1",
doi = "10.1016/j.juro.2012.02.2554",
language = "English",
volume = "188",
pages = "276--286",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer

AU - shiota, masaki

AU - takeuchi, ario

AU - Yokomizo, Akira

AU - Kashiwagi, Eiji

AU - Tatsugami, Katsunori

AU - Kuroiwa, Kentaro

AU - Naito, Seiji

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Purpose: There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer. Materials and Methods: We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines. Results: AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance. Conclusions: AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.

AB - Purpose: There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer. Materials and Methods: We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines. Results: AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance. Conclusions: AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.

UR - http://www.scopus.com/inward/record.url?scp=84862146158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862146158&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2012.02.2554

DO - 10.1016/j.juro.2012.02.2554

M3 - Article

VL - 188

SP - 276

EP - 286

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 1

ER -