The online version of this article (doi:10.1186/1476-4598-11-54) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing of interests.
MY and CH designed the study. MY, FY and ZC performed the experiments and analysed and interpreted the results. PL and AC provided technical and material support. MY wrote the manuscript. PL and SL revised the manuscript. CH supervised the study. All authors read and approved the final manuscript.
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.
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.
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.
Additional file 1: Figure S1. In HCT116 p53−/− cells, Nutlin-3 could not decrease IBP expression. IBP expression was detected by western blot when HCT116 p53−/− cells were treated with different concentration of Nutlin-3 for 8 h. (TIFF 868 KB)12943_2012_1025_MOESM1_ESM.tiff
Additional file 2: Figure S2. IBP expression is not increase in response to cisplatin within 96 h in MCF-7 cells. IBP and p53 expression was detected by western blot when MCF-7 cells were treated with 8 μg/ml cisplatin continuously for 12 h to 96 h. (TIFF 744 KB)12943_2012_1025_MOESM2_ESM.tiff
Additional file 3: Figure S3. Quantification analysis for p21 expression in IBP-over-expressing MCF-7 cells treated with Ly294002 or wortmannin for 24 h. (TIFF 285 KB)12943_2012_1025_MOESM3_ESM.tiff
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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
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