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An Orthotopic Bladder Cancer Model for Gene Delivery Studies
07:48

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

Published on: December 1, 2013

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

Masaki Shiota1, Ario Takeuchi, Akira Yokomizo

  • 1Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The Journal of Urology
|May 22, 2012
PubMed
Abstract

Insights

Androgen receptor (AR) expression in bladder cancer inversely correlates with disease severity. Blocking AR signaling inhibits cancer growth and enhances doxorubicin sensitivity, suggesting AR as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Androgen receptor (AR) presence in bladder cancer is reported, but its expression and signaling role remain unclear.
  • Investigating AR expression and signaling is crucial for understanding bladder cancer progression and treatment.

Purpose of the Study:

  • To investigate androgen receptor (AR) expression in bladder cancer.
  • To elucidate the role of androgen/androgen receptor signaling in bladder cancer cell growth and drug sensitivity.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qPCR) assessed AR mRNA expression in bladder cancer tissues.
  • In vitro and in vivo studies evaluated AR's role in cell lines, including growth, drug sensitivity, and tumor suppression via castration.

Main Results:

  • AR mRNA expression showed an inverse correlation with bladder cancer grade, stage, and spread.
  • Androgen/androgen receptor signaling blockade decreased cell growth, colony formation, and viability in AR-expressing cell lines (UMUC3, MBT-2).
  • AR expression correlated with doxorubicin resistance; AR deprivation/knockdown sensitized cells to doxorubicin.

Conclusions:

  • AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics.
  • Androgen/androgen receptor signaling significantly impacts the growth and doxorubicin vulnerability of AR-expressing bladder cancer cells.
  • Targeting androgen/androgen receptor signaling presents a potential prophylactic and therapeutic strategy for AR-expressing bladder cancer.

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