Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas.
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.
Jang
Tae Jung
TJ
Department of Pathology, College of Medicine, Dongguk University, Gyeongju, Gyeongbuk 780-714, South Korea. taejung@mail.dongguk.ac.kr
Cha
Woo Heon
WH
Lee
Kyung Seob
KS
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
D015820:Cadherins; D034741:RNA, Small Interfering; D051546:Cyclooxygenase 2