Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells.
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.
Department of Clinical Biochemistry, Third Military Medical University, Chongqing, People's Republic of China.
Mingzhen
M
Yang
Fang
F
Yuan
Peng
P
Li
Zhongjiao
Z
Chen
An
A
Chen
Shuhui
S
Li
Chuanmin
C
Hu
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; C479750:DEF6 protein, human; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin