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Submitted on December 18, 2003
Proteomics in Cancer, Danish Cancer Society, Copenhagen Ø DK-2100
Corresponding Author: jom{at}cancer.dk
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
Revised on January 21, 2004
Accepted on January 21, 2004
Expression of the tumor suppressor protein 14-3-3
is down regulated in invasive transitional cell carcinomas of the urinary bladder undergoing epithelial to mesenchymal transition
, 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 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 is down-regulated in invasive TCCs, particularly in lesions that are undergoing epithelial to mesenchymal conversion. Altered expression of 14-3-3 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 expression is not associated with increased levels of the dominant-negative transcriptional regulator 
Np63. Down-regulation of 14-3-3 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 is highly up-regulated in pure squamous cell carcinomas. Taken together, these results provide evidence that deregulation of 14-3-3 may play a key role in bladder cancer progression, in particular in differentiation events leading to epithelial/mesenchymal transition and stratified squamous metaplasia.
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