Abstract
The 14-3-3 proteins constitute a family of abundant, highly conserved and broadly expressed acidic polypeptides that are involved in the regulation of various cellular processes such as cell-cycle progression, cell growth, differentiation, and apoptosis. One member of this family, the 14-3-3 isoform sigma, is expressed only in epithelial cells and is frequently down-regulated in a variety of human cancers. To determine the prevalence of 14-3-3 sigma silencing in bladder cancer progression, we have studied the expression of this protein in normal urothelium and bladder transitional cell carcinomas (TCCs) of various grades and stages using two-dimensional gel electrophoresis in combination with Western blotting and immunohistochemistry. We show that the expression of 14-3-3 sigma is down-regulated in invasive TCCs, particularly in lesions that are undergoing epithelial-to-mesenchymal conversion. Altered expression of 14-3-3 sigma in invasive TCCs is not due to increased externalization of the protein nor to an aberrant proliferative potential of neoplastic cells. Furthermore, we found that impaired 14-3-3 sigma expression is not associated with increased levels of the dominant-negative transcriptional regulator Delta Np63. Down-regulation of 14-3-3 sigma was confirmed by indirect immunofluorescence using a peptide-based rabbit polyclonal antibody specific for this protein. We also show that the expression of 14-3-3 sigma is highly up-regulated in pure squamous cell carcinomas. Taken together, these results provide evidence that deregulation of 14-3-3 sigma may play a key role in bladder cancer progression, in particular in differentiation events leading to epithelial-to-mesenchymal transition and stratified squamous metaplasia.
| Original language | English |
|---|---|
| Journal | Molecular and Cellular Proteomics |
| Volume | 3 |
| Issue number | 4 |
| Pages (from-to) | 410-9 |
| Number of pages | 10 |
| ISSN | 1535-9476 |
| DOIs | |
| Publication status | Published - 2004 |
| Externally published | Yes |
Keywords
- 14-3-3 Proteins
- Blotting, Western
- Carcinoma, Squamous Cell
- Carcinoma, Transitional Cell
- Cell Differentiation
- Cell Division
- Cells, Cultured
- Down-Regulation
- Electrophoresis, Gel, Two-Dimensional
- Epithelial Cells
- Fluorescent Antibody Technique, Indirect
- Gene Silencing
- Genes, Dominant
- Genes, Tumor Suppressor
- Humans
- Immunoenzyme Techniques
- Mesoderm
- Neoplasm Invasiveness
- Proteomics
- Tyrosine 3-Monooxygenase
- Urinary Bladder
- Urinary Bladder Neoplasms
- Urinary Tract
