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 language | English |
|---|---|
| Pages (from-to) | 276-286 |
| Number of pages | 11 |
| Journal | Journal of Urology |
| Volume | 188 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 1 2012 |
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All Science Journal Classification (ASJC) codes
- Urology
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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 journal › Article
}
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 -