Upregulation of REG Iα accelerates tumor progression in pancreatic cancer with diabetes

Authors

  • Lin Zhou,

    1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Ruifeng Zhang,

    1. Department of Respiratory medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Lishun Wang,

    1. Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Shaoming Shen,

    1. Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Hiroshi Okamoto,

    1. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Akira Sugawara,

    1. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Li Xia,

    1. Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Xiaoling Wang,

    1. Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Naoya Noguchi,

    1. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Takeo Yoshikawa,

    1. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Akira Uruno,

    1. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan
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  • Weiyan Yao,

    1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Yaozong Yuan

    Corresponding author
    1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    • Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
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    • Tel/Fax: +[86-21-64150773]


Abstract

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.

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