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

Yamashita,Takahisa; Higashi,Morihiro; Momose,Shuji; Morozumi,Makoto; Tamaru,Jun-Ichi

doi:10.3892/ijo.2017.4031

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

Authors:
- Takahisa Yamashita
- Morihiro Higashi
- Shuji Momose
- Makoto Morozumi
- Jun-Ichi Tamaru
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Affiliations: Department of Pathology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama 350-8550, Japan, Department of Urology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama 350-8550, Japan
Published online on: June 7, 2017 https://doi.org/10.3892/ijo.2017.4031
Pages: 579-586

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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.

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