The interrelationships between Src, Cav-1 and RhoGD12 in transitional cell carcinoma of the bladder

Br J Cancer. 2012 Mar 13;106(6):1187-95. doi: 10.1038/bjc.2012.52. Epub 2012 Feb 21.

Abstract

Background: The aim of this current study was to assess the expression and activity of Src family kinases, focal adhesion kinase (FAK), caveolin (Cav-1) and RhoGD12 in bladder cancer.

Methods: Fifty-eight patients with a new diagnosis of bladder cancer undergoing transurethral resection were included. Immunohistochemical staining was utilised to assess expression of c-Src, dephosphorylated (SrcY(530)), phosphorylated Src (Y(419)), phosphorylated FAK (FAK Y(861)), Cav-1 and RhoGD12. Expression was assessed using the weighted histoscore method.

Results: High expression of dephosphorylated Y(527), phosphorylated Y(416) and phosphorylated FAK Y(861) in the membrane were associated with increased cancer-specific survival (P=0. 01, P=0.001, P=0.008, respectively) and expression of Y(416) in the membrane was an independent factor on multivariate analysis when combined with known clinical parameters (P=0.008, HR 0.288, 95% CI 0.11-0.72).

Conclusion: These results demonstrate that in contrast to other solid tumours, activation of the Src family members and downstream signalling proteins are associated with a good prognosis in transitional cell carcinoma of the bladder, and activated Src has a positive relationship with RhoGD12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Enzyme Activation
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Phosphorylation
  • Prognosis
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • src-Family Kinases

Substances

  • CAV1 protein, human
  • Caveolin 1
  • Guanine Nucleotide Dissociation Inhibitors
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases
  • CSK protein, human