Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells

Tumour Biol. 2015 Feb;36(2):1155-62. doi: 10.1007/s13277-014-2625-2. Epub 2014 Oct 22.

Abstract

Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells and the relationship with POK erythroid myeloid ontogenic factor (Pokemon). TGF-β1 and its receptors mediate several tumorigenic cascades that regulate cell proliferation, migration, and survival of bladder cancer cells. Bladder cancer cells T24 were treated with different levels of TGF-β1. Levels of Pokemon, E-cadherin, Snail, MMP2, MMP9, Twist, VEGF, and β-catenin messenger RNA (mRNA) and protein were examined by real-time quantitative fluorescent PCR and Western blot analysis, respectively. The effects of TGF-β1 on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay, proliferation of T24 was evaluated with reference to growth curves with MTT assay, and cell invasive ability was investigated by Transwell assay. Data show that Pokemon was inhibited by TGF-β1 treatment; the gene and protein of E-cadherin and β-catenin expression level showed decreased markedly after TGF-β1 treatment (P < 0.05). While the bladder cancer cell after TGF-β1 treatment showed a significantly reduced wound-closing efficiency at 6, 12, and 24 h, mechanistic analyses demonstrated that different levels of TGF-β1 promotes tumor cell growth, migration, and invasion in bladder cancer cells (P < 0.01, P < 0.05, respectively). In summary, our findings suggest that TGF-β1 may inhibit the expression of Pokemon, β-catenin, and E-cadherin. The high expression of TGF-β1 leads to an increase in the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Related mechanism is worthy of further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cadherins / biosynthesis
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Neoplasm Proteins / biosynthesis*
  • RNA, Messenger / biosynthesis
  • Transcription Factors / biosynthesis*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / administration & dosage
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Wound Healing
  • beta Catenin / biosynthesis

Substances

  • Cadherins
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Transcription Factors
  • Transforming Growth Factor beta1
  • ZBTB7A protein, human
  • beta Catenin