Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility
Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility
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DOI：
10.1038/labinvest.2009.5
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发表时间：
2009-04-01
影响因子：
5
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Yamazaki, Ken;Takamura, Masaaki;Sakamoto, Michiie
胰腺癌由于其早期诊断的困难和侵袭性，在癌症中预后最差。为了表征胰腺癌对基因表达的侵袭性，将胰腺癌异种移植物移植到严重联合免疫缺陷小鼠中作为基因表达谱的面板。作为分析的结果，腺苷酸环化酶相关蛋白1（CAP1）基因显示在所有异种移植物中过表达。免疫组化检测73例胰腺癌组织中CAP1蛋白的表达。临床标本中CAP 1阳性肿瘤细胞的比例与淋巴结转移和神经侵袭的存在相关，也与患者的不良预后相关。胰腺癌细胞的免疫细胞化学分析表明，CAP1与肌动蛋白共定位于板状伪足的前缘。通过RNA干扰敲低CAP1导致胰腺癌细胞的板状伪足形成、运动和侵袭减少。这是第一份证明CAP1在胰腺癌中过表达的报告，并表明CAP1参与胰腺癌细胞的侵袭行为。
Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.