Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells.
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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干扰素调节因子 4 结合蛋白是一种新型 p53 靶基因，可抑制顺铂诱导的乳腺癌细胞凋亡。
DOI：
10.1186/1476-4598-11-54
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发表时间：
2012-08-13
期刊：
影响因子：
37.3
通讯作者：
Hu C
中科院分区：
文献类型：
--
作者：
Yang M;Yuan F;Li P;Chen Z;Chen A;Li S;Hu C
我们以前的工作表明干扰素调节因子4结合蛋白（IBP）的异位表达与人乳腺癌细胞的恶性行为相关。控制乳腺癌中IBP差异表达的机制仍不清楚。为了探讨乳腺癌中IBP表达异常的机制，我们发现IBP是一个新的p53靶基因。IBP表达受野生型p53负调控，并受DNA损伤剂顺铂依赖性抑制。此外，发现高水平的IBP减少顺铂诱导的生长抑制和凋亡性细胞死亡，这与p53活性降低和Bcl-2家族成员表达不平衡有关。IBP是一个新的p53靶基因，通过负反馈调节p53信号通路抑制顺铂介导的乳腺癌细胞凋亡，提示IBP可能作为药物干预顺铂耐药乳腺癌的靶点。
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.
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