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We previously demonstrated that overexpression of CA2 was associated with invasion and progression of urothelial carcinoma (UC) in humans. The purpose of the present study was to evaluate the effects of the CA inhibitor acetazolamide (Ace) on <jats:italic>N<\/jats:italic>\u2010butyl\u2010<jats:italic>N<\/jats:italic>\u2010(4\u2010hydroxybutyl)nitrosamine (BBN)\u2010induced bladder carcinogenesis in mice and explore the function of CA2 in muscle invasion by UC. Male mice were treated with 0.025% (experiment 1) or 0.05% BBN (experiment 2) in their drinking water for 10\u2009weeks, then treated with cisplatin (Cis), Ace, or Cis plus Ace for 12\u2009weeks. In experiment 1, the overall incidence of BBN\u2010induced UCs was significantly decreased in the BBN\u2192Ace and BBN\u2192Cis+Ace groups. In experiment 2, the overall incidence of BBN\u2010induced UCs was significantly decreased in the BBN\u2192Cis+Ace group, and the incidence of muscle invasive UC was significantly decreased in both the BBN\u2192Ace and the BBN\u2192Cis+Ace groups. We also show that overexpression of CA2 by human UC cells T24 and UMUC3 significantly increased their migration and invasion capabilities, and that Ace significantly inhibited migration and invasion by CA2\u2010overexpressing T24 and UMUC3 cells. These data demonstrate a functional association of CA2 with UC development and progression, confirming the association of CA2 with UC that we had shown previously by immunohistochemical analysis of human UC specimens and proteome analysis of BBN\u2010induced UC in rats. Our finding that inhibition of CA2 inhibits UC development and muscle invasion also directly confirms that CA2 is a potential therapeutic target for bladder cancers.<\/jats:p>","DOI":"10.1111\/cas.15467","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T10:26:18Z","timestamp":1655720778000},"page":"2642-2653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The carbonic anhydrase inhibitor acetazolamide inhibits urinary bladder cancers via suppression of \u03b2\u2010catenin signaling"],"prefix":"10.1111","volume":"113","author":[{"given":"Taisuke","family":"Matsue","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology Osaka Metropolitan University, Graduate School of Medicine  Osaka Japan"},{"name":"Department of Urology Osaka City University, Graduate School of Medicine  Osaka 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