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-cadherin immunoreactivity and tumor aggressiveness. However, the mechanisms leading to decreased E-cadherin immunoreactivity are still unclear. Comparison of Northern blotting and immunohistochemistry in a series of 49 frozen bladder tumors revealed that, in 16 of 23 tumors with abnormal staining, clear mRNA down-regulation occurred. In the 7 cases without mRNA down-regulation, no structural anomalies of E-cadherin could be detected by Southern blotting, Western blotting or PCR-SSCP. Western blotting confirmed that, in 6 of these tumors, E-cadherin was down-regulated at the protein level. This down-regulation was accompanied by down-regulation of alpha-catenin and, to a lesser extent, of beta- or gamma-catenin. However, Northern-blot analysis indicated that expression of the 3 catenins is maintained at the mRNA level. Thus our data show that, in bladder tumors, mRNA down-regulation accounts for about two thirds (16/23) of tumors with abnormal staining and that post-transcriptional down-regulation of E-cadherin occurs in 6/23 of these tumors.
Bringuier
P P
PP
Urological Research Laboratory, University Hospital Nijmegen, Nijmegen, The Netherlands.
Giroldi
L A
LA
Umbas
R
R
Shimazui
T
T
Schalken
J A
JA
D015152:Blotting, Northern; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D009363:Neoplasm Proteins; D012333:RNA, Messenger