title: Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas.
abstract: Carcinoma cells become more motile and invasive via downmodulation of E-cadherin. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis. The aim of this study is to investigate the relationship between the expression of COX-2 and E-cadherin in a bladder cancer cell line and human bladder transitional cell carcinoma (TCCs). Phorbol 12-myristate 13-acetate (PMA) treatment for 5637 bladder cancer cells increased COX-2 expression, slightly induced Slug expression, and decreased E-cadherin expression. Ectopic expression of COX-2 or prostaglandin E(2) (PGE(2)) treatment for 5637 cells reduced E-cadherin expression. This finding was confirmed by the result that knockdown of COX-2 expression or indomethacin administration increased the expression of E-cadherin. When compared with cells' motility in serum-free medium, the treatment of PMA and PGE(2) increased cell motility, and indomethacin treatment slightly decreased cell motility. In the tissues of bladder TCCs, COX-2 expression was inversely correlated with membranous E-cadherin expression and positively correlated with nuclear beta-catenin expression. The expression of COX-2 and nuclear beta-catenin expression was significantly higher in TCCs of high grade and invasive growth than in TCCs of low grade and noninvasive growth. In contrast, membranous E-cadherin expression was more decreased in tumors of high grade and invasive growth. In addition, nuclear beta-catenin expression was significantly related to tumor recurrence. We suggest that COX-2 pathway reduces membranous E-cadherin expression in bladder TCCs and their expression pattern may provide important information in predicting the clinical behavior of bladder TCCs.
authors.affiliation: Department of Pathology, College of Medicine, Dongguk University, Gyeongju, Gyeongbuk 780-714, South Korea. taejung@mail.dongguk.ac.kr
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Jang
authors.forename: Woo Heon
authors.initials: WH
authors.lastname: Cha
authors.forename: Kyung Seob
authors.initials: KS
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D034741:RNA, Small Interfering; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; D051546:Cyclooxygenase 2