Upregulation of REG Iα accelerates tumor progression in pancreatic cancer with diabetes
Upregulation of REG Iα accelerates tumor progression in pancreatic cancer with diabetes
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DOI：
10.1002/ijc.25188
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发表时间：
2010-10
影响因子：
6.4
通讯作者：
Lin Zhou;Ruifeng Zhang;Lishun Wang;Shaoming Shen;H. Okamoto;A. Sugawara;L. Xia;Xiaoling Wang;N. Noguchi;T. Yoshikawa;A. Uruno;W. Yao;Yao-zong Yuan
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文献类型：
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作者：
Lin Zhou;Ruifeng Zhang;Lishun Wang;Shaoming Shen;H. Okamoto;A. Sugawara;L. Xia;Xiaoling Wang;N. Noguchi;T. Yoshikawa;A. Uruno;W. Yao;Yao-zong Yuan
糖尿病现在被普遍认为是胰腺癌(PAC)过程中的一个关键事件。然而，糖尿病和PAC之间潜在的分子机制还不完全清楚。再生基因(Reg)Iα是一种影响胰岛β细胞的生长因子，已被证明与胃肠道肿瘤的发生有关。因此，有理由推测Reg Iα在糖尿病合并PAC的发病机制中可能起重要作用。本研究的目的是评估Reg Iα蛋白在合并和不合并糖尿病的PAC中的表达情况，并确定Reg Iα在PAC发生发展中的作用。通过免疫印迹实验发现，α蛋白在糖尿病帕金森病患者的癌组织中优先表达。免疫组织化学分析显示，糖尿病组(n=38)Reg Iα阳性癌细胞显著高于非糖尿病组(n=42，p<0.05)。此外，我们发现，在PAC细胞系中过表达Reg Iα蛋白导致细胞增殖加速，从而导致肿瘤在体外和体内的生长。这些发现表明，REG Iα可能是肿瘤的促进剂之一，并有助于PAC的侵袭性，特别是在糖尿病患者亚群中。这项研究将为理解糖尿病和PAC之间联系的分子机制提供新的见解。
Diabetes is now generally accepted as a crucial event in the process of pancreatic cancer (PaC). However, molecular mechanisms underlying the relationship between diabetes and PaC are not fully understood. Regenerating gene (REG) Iα is a growth factor affecting pancreatic islet beta cells, and it has been shown to be involved in the carcinogenesis in gastrointestinal tract. It is rational to speculate that REG Iα plays a potential role in the pathogenesis of PaC with diabetes. The aim of this study was to evaluate the REG Iα protein expression profile in PaC with and without diabetes, and define the contribution of REG Iα on PaC development. We found that REG Iα protein preferentially expressed in cancerous tissues of PaC patients with diabetes by Western blot. REG Iα positive cancer cells in PaC with diabetes (n = 38) was significantly higher than that in subjects without diabetes (n = 42, p < 0.05) by immunohistochemical analysis. Furthermore, we found that overexpression of REG Iα protein in PaC cell lines resulted in accelerated cell proliferation and consequently tumor growth, both in vitro and in vivo. The findings suggest that REG Iα may act as one of the tumor promoter and contribute to the aggressive nature of PaC, especially in the subpopulation with diabetes. This study would shed new insights for understanding the molecular mechanisms underlying the link between diabetes and PaC.