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Mechanisms associated with abnormal E-cadherin immunoreactivity in human bladder tumors
P P Bringuier1, L A Giroldi, R Umbas
1Urological Research Laboratory, University Hospital Nijmegen, Nijmegen, The Netherlands.
International Journal of Cancer
|October 16, 1999
Summary
Decreased E-cadherin in bladder tumors is often due to mRNA down-regulation. In some cases, post-transcriptional changes also reduce E-cadherin protein levels, impacting tumor aggressiveness.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- E-cadherin is crucial in carcinoma progression, with decreased levels correlating to tumor aggressiveness.
- The precise mechanisms behind reduced E-cadherin levels in tumors remain largely unknown.
Purpose of the Study:
- To investigate the mechanisms of E-cadherin down-regulation in bladder tumors.
- To differentiate between transcriptional and post-transcriptional regulation of E-cadherin.
Main Methods:
- Comparative analysis of Northern blotting and immunohistochemistry in 49 bladder tumors.
- Utilized Southern blotting, Western blotting, and PCR-SSCP to assess E-cadherin gene and protein expression.
- Examined the expression of alpha-, beta-, and gamma-catenin.
Main Results:
- mRNA down-regulation was observed in 16 out of 23 tumors with abnormal E-cadherin staining.
- Post-transcriptional down-regulation of E-cadherin protein occurred in 6 tumors without mRNA reduction.
- Down-regulation of alpha-catenin and, to a lesser extent, beta/gamma-catenin accompanied E-cadherin protein reduction.
Conclusions:
- mRNA down-regulation accounts for the majority (approx. 2/3) of abnormal E-cadherin staining in bladder tumors.
- Post-transcriptional mechanisms contribute to E-cadherin down-regulation in a subset of bladder tumors.
- Altered catenin expression suggests broader impacts on cell adhesion in bladder carcinoma.