Upregulation of the splice variant MUC4/Y in the pancreatic cancer cell line MIA PaCa-2 potentiates proliferation and suppresses apoptosis: new insight into the presence of the transcript variant of MUC4.
Upregulation of the splice variant MUC4/Y in the pancreatic cancer cell line MIA PaCa-2 potentiates proliferation and suppresses apoptosis: new insight into the presence of the transcript variant of MUC4.
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DOI：
10.3892/or.2014.3113
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发表时间：
2014-05
期刊：
影响因子：
4.2
通讯作者：
Kunling Xie;X. Zhi;Jie Tang;Yi Zhu;Jing-Jing Zhang-Jing;Zheng Li;Jinqiu Tao;Zekuan Xu
中科院分区：
文献类型：
--
作者：
Kunling Xie;X. Zhi;Jie Tang;Yi Zhu;Jing-Jing Zhang-Jing;Zheng Li;Jinqiu Tao;Zekuan Xu
MUC4的转录物变体4 MUC4/Y与MUC4的转录物变体1相比缺少外显子2。迄今为止，关于MU4/Y功能的直接证据仍有待报道。以往的研究基于MUC4/Y的特征结构域对其功能的假设。本研究的目的是探讨MUC4/Y的具体功能。以MUC4/Y低表达的胰腺癌细胞系MIA PaCa-2为研究对象，利用慢病毒载体系统建立MUC4/Y稳定上调的细胞模型。结果表明，MUC4/Y锚定在细胞膜上，影响细胞形态和细胞周期。功能分析表明，MUC4/Y的上调在体内和体外均能轻微增强细胞增殖，显著抑制细胞凋亡。进一步的研究表明，JNK和AKT信号通路被激活。同时，MUC4/Y的上调对MUC4的膜伴侣HER2的磷酸化水平影响甚微。这些结果表明，MUC4/Y通过其对MIA PaCa-2细胞的抗凋亡和弱有丝分裂作用促进肿瘤进展。
MUC4/Y, the transcript variant 4 of MUC4, lacks exon 2 as compared with the transcript variant 1 of MUC4. To date, direct evidence for the function of MU4/Y remains to be reported. Previous studies based their hypotheses regarding the function of MUC4/Y on the characteristic structure domains of this variant. The aim of the present study was to investigate the specific function of MUC4/Y. The pancreatic cancer cell line MIA PaCa-2 with low MUC4/Y expression was used to establish a stable cell model of MUC4/Y upregulation using a lentivirus vector system. Results showed that MUC4/Y anchored on the cytomembrane and affected cell morphology and cell cycle. Functional analyses indicated that MUC4/Y upregulation slightly potentiated cell proliferation and significantly suppressed apoptosis both in vivo and in vitro. Further studies revealed that the JNK and AKT signalling pathways were activated. Meanwhile, MUC4/Y upregulation elicited minimal effect on the phosphorylation level of HER2, a membrane partner of MUC4. These results suggest that MUC4/Y promotes tumour progression through its anti-apoptotic and weak mitogenic effect on MIA PaCa-2 cells.