Nuclear expression of Y box binding-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer

Int J Oncol. 2017 Aug;51(2):579-586. doi: 10.3892/ijo.2017.4031. Epub 2017 Jun 7.

Abstract

The development and acquisition of multiple drug resistance in cancer cells remain a major obstacle in the treatment of bladder cancer. Nuclear translocation of Y box binding-1 (YB-1), which is a member of a family of DNA-binding proteins that contain a cold shock domain, plays a significant role in the acquisition of drug resistance by upregulating expression of the multidrug resistance-1 (MDR-1) gene product, p-glycoprotein. The tumor suppressor protein p53 is thought to be essential for nuclear translocation of YB-1. We hypothesized that nuclear translocation of YB-1 might be associated with drug resistance of bladder cancer with an abnormality of the TP53 gene that results in a mutated p53 protein. To test this hypothesis, we analyzed the association of YB-1 with drug resistance of TP53-mutated bladder cancer, including immunohistochemical analysis of YB-1, p-glycoprotein and p53 in vivo as well as the function of YB-1 nuclear translocation and regulation of its translocation by p53 in vitro. Additionally, we examined the association between the nuclear translocation of YB-1 and gemcitabine, a major anticancer-drug for bladder cancer, in cancer cell lines. Nuclear expression of YB-1 was correlated with the expression of p-glycoprotein and p53 in bladder cancer cases (p<0.05). In vitro, both introduction of TP53 and gemcitabine induced nuclear translocation of YB-1. These data indicate that YB-1 translocates to the nucleus coordinately with p53 expression and is involved in gemcitabine resistance in bladder cancer. Nuclear expression of YB-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Deoxycytidine / analogs & derivatives
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm*
  • Female
  • Gemcitabine
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Mutation
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • Deoxycytidine
  • Gemcitabine