Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells

BJU Int. 2011 Jul;108(2 Pt 2):E142-9. doi: 10.1111/j.1464-410X.2010.09810.x. Epub 2010 Nov 17.

Abstract

Objective: To investigate the roles of Twist1 and Y-box binding protein-1 (YB-1) and their potential as therapeutic targets in bladder cancer (BC), as both have been suggested to play important roles in tumour growth, invasion and drug resistance.

Materials and methods: Bladder cancer cell lines (TCCsup, UMUC3, T24 and KK47 cells) were used. Twist1 and YB-1 expression levels were assessed by luciferase reporter assay, quantitative real-time polymerase chain reaction (PCR) and western blot analysis. Tumour growth and cell cycle were analysed by cell proliferation assay and flow cytometry, respectively. Invasive and motile abilities were investigated by scratch-wound test and migration assay, respectively. Cytotoxicity assay was performed to determine drug sensitivity.

Results: The findings showed that Twist1 regulated YB-1 expression in BC cells. Both Twist1 and YB-1 were involved in cell growth, invasion, motility and resistance to cisplatin and doxorubicin, but not to 5-fluorouracil (5-FU).

Conclusion: The present study showed that Twist1 regulates YB-1 expression and that both Twist1 and YB-1 promote malignant potentials, including tumour growth, invasion and anti-cancer-drug resistance, indicating that both Twist1 and YB-1 are novel molecular targets in BC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biological Assay
  • Blotting, Western
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Doxorubicin / pharmacology
  • Fluorouracil / pharmacology
  • Humans
  • Nuclear Proteins / drug effects
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Twist-Related Protein 1 / drug effects
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Urinary Bladder Neoplasms / metabolism*
  • Y-Box-Binding Protein 1 / drug effects
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Y-Box-Binding Protein 1
  • Doxorubicin
  • Cisplatin
  • Fluorouracil