NT5E and FcGBP as key regulators of TGF-1-induced epithelial-mesenchymal transition (EMT) are associated with tumor progression and survival of patients with gallbladder cancer

Cell Tissue Res. 2014 Feb;355(2):365-74. doi: 10.1007/s00441-013-1752-1. Epub 2013 Dec 6.


Epithelial-mesenchymal transitions (EMTs) are essential manifestations of epithelial cell plasticity during tumor progression. Transforming growth factor-β(TGF-β) modulates epithelial plasticity in tumor physiological contexts by inducing EMT, which is associated with the altered expression of genes. In the present study, we used DNA micro-array analysis to search for differentially expressed genes in the TGF-β1 induced gallbladder carcinoma cell line (GBC-SD cells), as compared with normal GBC-SD cells. We identified 225 differentially expressed genes, including 144 that were over-expressed and 81 that were under-expressed in the TGF-β1 induced GBC-SD cells. NT5E (CD73) is the most increased gene, while the Fc fragment of the IgG binding protein (FcGBP) is the most decreased gene. The expression patterns of these two genes in gallbladder adenocarcinoma and chronic cholecystitis tissue were consistent with the micro-array data. Immunochemistry and clinicopathological results showed that the expression of NT5E and FcGBP in gallbladder adenocarcinoma is an independent marker for evaluation of the disease progression, clinical biological behaviors and prognosis. The data from the current study indicate that differential NT5E and FcGBP expressions could be further evaluated as biomarkers for predicting survival of patients with gallbladder cancer and that NT5E and FcGBP could be promising targets in the control of gallbladder cancer progression.

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism*
  • Blotting, Western
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Disease Progression*
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / metabolism*
  • Gallbladder Neoplasms / pathology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Small Interfering / metabolism
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Transforming Growth Factor beta1 / pharmacology*


  • Cell Adhesion Molecules
  • FCGBP protein, human
  • GPI-Linked Proteins
  • RNA, Small Interfering
  • Transforming Growth Factor beta1
  • 5'-Nucleotidase
  • NT5E protein, human