Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Int J Cancer. 2010 Oct 15;127(8):1795-803. doi: 10.1002/ijc.25188.
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) Ialpha 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 Ialpha plays a potential role in the pathogenesis of PaC with diabetes. The aim of this study was to evaluate the REG Ialpha protein expression profile in PaC with and without diabetes, and define the contribution of REG Ialpha on PaC development. We found that REG Ialpha protein preferentially expressed in cancerous tissues of PaC patients with diabetes by Western blot. REG Ialpha 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 Ialpha 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 Ialpha 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.
糖尿病现在被普遍认为是胰腺癌（PaC）发生过程中的一个关键事件。然而，糖尿病与 PaC 之间关系的分子机制尚不完全清楚。再生基因（REG）Ialpha 是一种影响胰腺胰岛β细胞生长的因子，它已被证明参与了胃肠道的癌变过程。合理推测 REG Ialpha 在伴糖尿病的 PaC 发病机制中发挥潜在作用。本研究旨在评估伴有和不伴有糖尿病的 PaC 中 REG Ialpha 蛋白的表达谱，并确定 REG Ialpha 对 PaC 发展的贡献。我们通过 Western blot 发现，REG Ialpha 蛋白在伴有糖尿病的 PaC 患者的癌组织中优先表达。通过免疫组织化学分析，我们发现伴有糖尿病的 PaC 患者（n = 38）中 REG Ialpha 阳性癌细胞明显高于无糖尿病患者（n = 42，p < 0.05）。此外，我们发现 PaC 细胞系中 REG Ialpha 蛋白的过表达导致细胞增殖加速，从而导致体外和体内肿瘤生长加速。这些发现表明，REG Ialpha 可能作为肿瘤促进剂之一，促进 PaC 的侵袭性，特别是在伴糖尿病的亚群中。本研究将为理解糖尿病与 PaC 之间联系的分子机制提供新的见解。
