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

TY - JOUR

T1 - 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

AU - Moreira, José Manuel Alfonso

AU - Gromov, Pavel

AU - Celis, Julio E

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - 14-3-3 Proteins

KW - Blotting, Western

KW - Carcinoma, Squamous Cell

KW - Carcinoma, Transitional Cell

KW - Cell Differentiation

KW - Cell Division

KW - Cells, Cultured

KW - Down-Regulation

KW - Electrophoresis, Gel, Two-Dimensional

KW - Epithelial Cells

KW - Fluorescent Antibody Technique, Indirect

KW - Gene Silencing

KW - Genes, Dominant

KW - Genes, Tumor Suppressor

KW - Humans

KW - Immunoenzyme Techniques

KW - Mesoderm

KW - Neoplasm Invasiveness

KW - Proteomics

KW - Tyrosine 3-Monooxygenase

KW - Urinary Bladder

KW - Urinary Bladder Neoplasms

KW - Urinary Tract

U2 - 10.1074/mcp.M300134-MCP200

DO - 10.1074/mcp.M300134-MCP200

M3 - Journal article

C2 - 14736829

SN - 1535-9476

VL - 3

SP - 410

EP - 419

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 4

ER -