AP1B plays an important role in intestinal tumorigenesis with the truncating mutation of an APC gene
AP1B plays an important role in intestinal tumorigenesis with the truncating mutation of an APC gene
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AP1B通过APC基因的截短突变在肠道肿瘤发生中发挥重要作用
DOI：
10.1002/ijc.26131
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
et al
中科院分区：
文献类型：
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作者：
Mimura;M.;et al
最近的证据表明癌症伴随着细胞极性的丧失。 AP-1 网格蛋白接头复合物的上皮细胞特异性形式 AP1B 参与膜蛋白向上皮细胞基底外侧表面的极化转运。在我们的研究中，我们研究了 AP1B 是否参与肠道肿瘤发生。使用 APCMin/+ 小鼠作为体内模型，并通过共聚焦显微镜检查具有腺瘤性息肉病 (APC) 基因截短突变的 SW480 细胞作为体外模型，检查肠道肿瘤细胞的细胞极性。接下来，通过实时聚合酶链反应（PCR）和蛋白质印迹法检测肠道肿瘤细胞中AP1B的表达。分别采用共聚焦显微镜和实时荧光定量PCR技术评估结直肠癌患者肿瘤组织中β-catenin的定位和AP1B的表达情况，并探讨细胞极性、AP1B表达与肠道肿瘤发生之间的关系。肠道肿瘤细胞细胞极性丧失，AP1B表达下调。此外，AP1B 表达水平的降低与人结直肠癌中 β-catenin 的核定位相关。我们的研究表明 AP1B、肠道肿瘤发生和 APC 基因突变之间存在密切关联。这是第一份揭示AP1B、细胞极性和肠道肿瘤发生之间关系的报告，对AP1B的详细了解有望导致肠癌治疗靶点和新型生物标志物的发现。
Recent evidence has suggested that carcinoma is accompanied by the loss of cell polarity. An epithelial cell‐specific form of the AP‐1 clathrin adaptor complex, AP1B, is involved in the polarized transport of membrane proteins to the basolateral surface of epithelial cells. In our study, we investigated whether AP1B is involved in intestinal tumorigenesis. The cellular polarity of intestinal tumor cells was examined using APCMin/+mice as anin vivomodel and SW480 cells with a truncating mutation in the adenomatous polyposis coli (APC) gene as anin vitromodel by confocal microscopy. Next, the expression of AP1B in intestinal tumor cells was examined by real‐time polymerase chain reaction (PCR) and Western blotting. The localization of β‐catenin and the expression of AP1B in the tumor tissue of patients with colorectal cancer were evaluated by confocal microscopy and real‐time PCR, respectively, and the relationships among cell polarity, AP1B expression and intestinal tumorigenesis were examined. Cellular polarity was lost in intestinal tumor cells, and the expression of AP1B was downregulated. In addition, the reduction in the expression level of AP1B correlated with the nuclear localization of β‐catenin in human colorectal cancer. Our study indicates the close associations between AP1B, intestinal tumorigenesis and mutations in the APC gene. This is the first report to reveal the relationships among AP1B, cellular polarity and intestinal tumorigenesis, and achieving a detailed understanding of AP1B will hopefully lead to discovery of therapeutic targets and novel biomarkers for intestinal cancer.