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首页> 外文期刊>Cell and Tissue Research >Cooperation among Numb, MDM2 and p53 in the development and progression of pancreatic cancer
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Cooperation among Numb, MDM2 and p53 in the development and progression of pancreatic cancer

机译：Numb，MDM2和p53在胰腺癌发生发展中的合作

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摘要

We study the expression of Numb, MDM2 and p53 for clinical significance in pancreatic cancer (PC) and their functional relationship in regulating biological behaviors of PC cells. IHC, IB and qRT-PCR were used to detect Numb, MDM2 and p53 expression in PC. Transfection and drug intervention were used to investigate their functional relationship in PC cells. IHC showed that Numb expression was negatively associated with tumor size, differentiation and UICC stage, while expression of MDM2 and p53 was positively associated with tumor T and UICC stages, respectively (P < 0.05). Numb was an independent prognostic indicator in PC (P < 0.05). Patients with Numb-positive expression or combined with MDM2-negative expression had a significantly better overall survival (P < 0.05). Altered expression of Numb can regulate wild-type but not mutant p53 expression, while MDM2 knockdown increased Numb but not mutant p53 protein level. Meanwhile, Numb knockdown increased chemoresistance but decreased activated p53 and cleaved-caspase-3 protein expression in gemcitabine-treated Capan-2 cells. Moreover, Numb co-immunoprecipitated with p53 to prevent p53 ubiquitin-dependent protein degradation and this ubiquitin-dependent regulation plays an important role in the coordinate function of these three proteins on cell invasion and migration in PC cells. Our study is the first to demonstrate the clinical significance and functional cooperation among Numb, MDM2 and p53 involved in the development and progression of PC.
机译：我们研究了Numb，MDM2和p53在胰腺癌（PC）中的临床意义及其在调节PC细胞生物学行为中的功能关系的表达。使用IHC，IB和qRT-PCR检测PC中Numb，MDM2和p53的表达。转染和药物干预被用来研究它们在PC细胞中的功能关系。 IHC显示Numb的表达与肿瘤的大小，分化程度和UICC阶段呈负相关，而MDM2和p53的表达与肿瘤的T和UICC阶段呈正相关（P <0.05）。 Numb是PC的独立预后指标（P <0.05）。 Numb阳性表达或与MDM2阴性表达合并的患者的总生存期明显更好（P <0.05）。 Numb的表达改变可以调节野生型，但不能调节突变体p53的表达，而MDM2敲低可以增加Numb，但不能调节突变体p53的蛋白水平。同时，Numb组合降低了吉西他滨处理的Capan-2细胞的化学抗性，但降低了活化的p53和caspase-3裂解蛋白的表达。此外，Numb与p53共同免疫沉淀以防止p53泛素依赖性蛋白质降解，而这种泛素依赖性调节在这三种蛋白质对PC细胞侵袭和迁移的协调功能中起着重要作用。我们的研究是第一个证明Numb，MDM2和p53在PC发生和发展中涉及的临床意义和功能合作。

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