Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors

Shuko Hata, Kazue Ise, Abdullah Azmahani, Sachiko Konosu-Fukaya, Keely May McNamara, Fumiyoshi Fujishima, Keiji Shimada, Koji Mitsuzuka, Yoichi Arai, Hironobu Sasano, Yasuhiro Nakamura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. Main methods The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). Key findings DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Significance Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalLife Sciences
Volume190
DOIs
Publication statusPublished - 2017 Dec 1

Keywords

  • AR
  • Bladder urothelial carcinoma
  • Steroid metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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