Expression of the tumor suppressor protein 14-3-3 sigma is down-regulated in invasive transitional cell carcinomas of the urinary bladder undergoing epithelial-to-mesenchymal transition
Research output: Contribution to journal › Journal article › Research › peer-review
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 |
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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 |
- 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
Research areas
ID: 41043725