Upregulation of REG Ialpha accelerates tumor progression in pancreatic cancer with diabetes.
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.
Zhou
Lin
L
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhang
Ruifeng
R
Wang
Lishun
L
Shen
Shaoming
S
Okamoto
Hiroshi
H
Sugawara
Akira
A
Xia
Li
L
Wang
Xiaoling
X
Noguchi
Naoya
N
Yoshikawa
Takeo
T
Uruno
Akira
A
Yao
Weiyan
W
Yuan
Yaozong
Y
D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051847:Lithostathine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D051847:Lithostathine; C497617:REG1A protein, human