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J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:402-9. doi: 10.1016/j.jsbmb.2014.07.011. Epub 2014 Jul 30.

The vitamin D system is deregulated in pancreatic diseases.

Author information

1
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Leitstelle 3Q, 1090 Vienna, Austria.
2
2nd Department of Pathology, Semmelweis University, Üllői út 93, 1091 Budapest, Hungary.
3
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Leitstelle 3Q, 1090 Vienna, Austria. Electronic address: enikoe.kallay@meduniwien.ac.at.
4
University Clinic of Visceral Surgery and Medicine, Inselspital University Hospital, 3010 Bern, Switzerland.

Abstract

The vitamin D system is deregulated during development and progression of several cancer types. Data on the expression of the vitamin D system in the diseased pancreas are missing. The aim of this study was to investigate the expression of the vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1), and the calcium-sensing receptor (CaSR), a vitamin D target gene, in the different regions of the pancreas in patients with chronic pancreatitis (n=6) and pancreatic ductal adenocarcinomas (PDAC) (n=17). We analyzed the expression of these genes at mRNA and protein level with quantitative real-time RT-PCR and immunostaining. mRNA expression of CYP24A1 and VDR was significantly increased in tumors compared with the adjacent non-tumorous tissue (p<0.01), while CaSR mRNA expression decreased. Both the VDR and the CaSR protein were highly expressed in the endocrine compared with the exocrine pancreas. In CP the CYP24A1 expression was highest in the endocrine pancreas, while in PDACs in the transformed ducts. In the PDAC patients CYP24A1 expression in the islets was significantly lower than in CP patients. Our data suggest that during ductal adenocarcinoma development the vitamin D system in the pancreas becomes deregulated on two levels: in the islets CYP24A1 expression decreases weakening the negative feedback regulation of the vitamin D-dependent insulin synthesis/secretion. In the transformed ducts CYP24A1 expression increases, impairing the antiproliferative effect of vitamin D in these cells.

KEYWORDS:

CYP24A1; CaSR; Chronic pancreatitis; Pancreatic cancer; Pancreatic ductal adenocarcinoma; VDR; Vitamin D

PMID:
25090635
PMCID:
PMC4217145
DOI:
10.1016/j.jsbmb.2014.07.011
[Indexed for MEDLINE]
Free PMC Article

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