Mechanisms associated with abnormal E-cadherin immunoreactivity in human bladder tumors

The involvement of E-cadherin in the progression of carcinoma is supported by a large number of studies showing an inverse relationship between E-cadh erin immunoreactivity and tumor aggressiveness, However, the mechanisms lea ding to decreased E-cadherin immunoreactivity are still unclear. Comparison of Northern blotting and immunohistochemistry in a series of 49 frozen bla dder tumors revealed that, in 16 of 23 tumors with abnormal staining, clear mRNA downregulation occurred. In the 7 cases without mRNA downregulation, no structural anomalies of E-cadherin could be detected by Southern blottin g, Western blotting or PCR-SSCP. Western blotting confirmed that, in 6 of t hese tumors, E-cadherin was down-regulated at the protein level. This down- regulation was accompanied by down-regulation of alpha-catenin and, to a le sser extent, of beta- or gamma-catenin. However, Northern-blot analysis ind icated that expression of the 3 catenins is maintained at the mRNA level. T hus our data show that, in bladder tumors, mRNA down-regulation accounts fo r about two thirds (16/23) of tumors with abnormal staining and that post-t ranscriptional down-regulation of E-cadherin occurs in 6/23 of these tumors . (C) 1999 Wiley-Liss, Inc.