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Digestive Diseases and Sciences

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01.12.2015 | Original Article

Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis

verfasst von: Guoxiao Yin, Jiao Du, Hui Cao, Xiulan Liu, Qianqian Xu, Ming Xiang

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2015

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Abstract

Background

Regenerating islet-derived 3 (Reg3) is abnormally expressed in several human digestive system diseases, including chronic pancreatitis (CP) and pancreatic cancer (PC).

Aim

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.

Conclusion

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.

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Titel: Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis
verfasst von: Guoxiao Yin
Jiao Du
Hui Cao
Xiulan Liu
Qianqian Xu
Ming Xiang
Publikationsdatum: 01.12.2015
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2015
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-015-3787-5

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