title: Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis.
abstract: BACKGROUND
  Regenerating islet-derived 3 (Reg3) is abnormally expressed in several human digestive system diseases, including chronic pancreatitis (CP) and pancreatic cancer (PC).
  
  
  OBJECTIVE
  The purpose of this study was to clarify the mechanism of the enhanced expression of Reg3 in inflammation-induced PC.
  
  
  METHODS
  C57BL/6 mice were treated with caerulein for 6 weeks to induce CP and then injected with pReg3g--a lentivirus system encoding for murine Reg3g--accompanied by dimethylbenzanthracene to induce PC. We detected pancreatic histopathological characteristics, tumor-related gene expression, inflammation-associated pathway activation, serum biochemical indicators, and immunological cell activities.
  
  
  RESULTS
  The mice that developed CP after caerulein treatment were marked by pronounced histologic lesions, elevated serum amylase levels, and activation of inflammation-related pathways. Mice given a high dose of pReg3g developed PC by 16 weeks, with recognizable tumors in the pancreas. While, both the low and high doses of pReg3g produced higher transcription of c-fos, k-ras, cytokeratin-19, and proliferating cell nuclear antigen, and a lower expression of caspase-3 compared to pNEG controls. Additionally, the higher dose of pReg3g increased the expressions of pSTAT3, NFκB (p65), and SOCS3 methylation during PC development. In addition, mice treated with pReg3g displayed higher levels of serum IL10 and TGFβ and suppressed T lymphocyte proliferation and DC function.
  
  
  CONCLUSIONS
  The comprehensive analysis suggests enhanced Reg3g expression exacerbates PC in inflammation-associated cancer progression. Reg3g appears to promote CP-related PC in mice through multiple mechanisms, involving enhanced transcription of pancreatic tumor markers, repression of anti-tumor immunity, and activation of STAT3/p65 signal transduction pathways.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Guoxiao
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. xiangming@mails.tjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
mesh_terms: D061354:Acinar Cells; D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology
chemical_list: D016207:Cytokines; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse
keywords: Apoptosis; Chronic pancreatitis; Immunological surveillance; Pancreatic cancer; Proliferation; Reg3g