title: The vitamin D system is deregulated in pancreatic diseases.
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.
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Leitstelle 3Q, 1090 Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Hummel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Leitstelle 3Q, 1090 Vienna, Austria.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, 1091 Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Borka
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Leitstelle 3Q, 1090 Vienna, Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Bajna
authors.affiliation: 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.
authors.forename: Enikö
authors.initials: E
authors.lastname: Kállay
authors.affiliation: University Clinic of Visceral Surgery and Medicine, Inselspital University Hospital, 3010 Bern, Switzerland.
authors.forename: Henrik Csaba
authors.initials: HC
authors.lastname: Horváth
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: C095550:CASR protein, human; D019394:Ki-67 Antigen; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; C579457:VDR protein, human; D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: CYP24A1; CaSR; Chronic pancreatitis; Pancreatic cancer; Pancreatic ductal adenocarcinoma; VDR; Vitamin D
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