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Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells

Mingzhen Yang1, Fang Yuan23, Peng Li1, Zhongjiao Chen1, An Chen1, Shuhui Li1 and Chuanmin Hu1*

Author Affiliations

1 Department of Clinical Biochemistry, Third Military Medical University, Chongqing, 400038, P.R. China

2 Department of Cell Biology, Third Military Medical University, Chongqing, 400038, P.R. China

3 Urology Institute of People’s Liberation Army, Southwest Hospital, Third Military Medical University, Chongqing, 400038, P.R. China

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Molecular Cancer 2012, 11:54  doi:10.1186/1476-4598-11-54

Published: 13 August 2012

Abstract

Background

Our previous work demonstrated that ectopic expression of interferon regulatory factor 4 binding protein (IBP) was correlated with the malignant behaviour of human breast cancer cells. The mechanisms controlling differential expression of IBP in breast cancer still remain unknown.

Results

To investigate the mechanism of IBP dysregulation in breast cancer, we identified IBP was a novel p53 target gene. IBP expression was negatively regulated by wild-type p53 and was p53 dependently suppressed by DNA damage agent cisplatin. Furthermore, high levels of IBP were found to decrease cisplatin-induced growth suppression and apoptotic cell death, which was associated with decreased p53 activity and imbalanced Bcl-2 family member expression.

Conclusions

IBP is a novel p53 target gene which suppresses cisplatin-mediated apoptosis of breast cancer cells via negative feedback regulation of the p53 signalling pathway, suggesting IBP may serve as a target for pharmacologic intervention of breast cancer resistant to cisplatin therapy.

Keywords:
Breast cancer; Interferon regulatory factor 4 binding protein (IBP); p53; Cisplatin; Apoptosis