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Pancreatic Cancer massively deregulates the local Vitamin D receptors and CPY24A1 – July 2014

The vitamin D system is deregulated in pancreatic diseases

The Journal of Steroid Biochemistry and Molecular Biology, online 30 July 2014, DOI: 10.1016/j.jsbmb.2014.07.011
Doris Hummela, 1, Abhishek Aggarwala, 1, Katalin Borkab, Erika Bajnaa, Enikö Kállaya, , , Henrik Csaba Horvathc
Image
     shaded text and numbers in the chart were added by VitaminDWiki

Highlights

  • During PDAC development CYP24A1 levels are reduced in the endocrine islets.
  • During malignant transformation pancreatic ducts accumulate CYP24A1 protein.
  • CYP24A1 expression correlates with VDR in CP patients, but not in PDAC patients.
  • CYP24A1 overexpressing tumors are highly proliferative.
  • CaSR and VDR are co-expressed in the endocrine cells of the islets.

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 < 0.05), 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.

Tiny portions of the PDF

1. Introduction
Diseases of the pancreas represent a large burden both for patients and for the public health system.
Pancreatic cancer has poor clinical outcome, the 5-year survival rate is less than 6% (http://www.pancreatic.org ).
The management and follow-up of these patients are still a major challenge for health care providers.
Despite of relatively low incidence, death due to pancreatic cancer ranks fourth among cancer-related deaths in the Western world due to the poor survival rate and rapid fatality after diagnosis.
3. Results
MRNA expression of VDR, CYP24A1, and CaSR in pancreatic ductal adenocarcinoma (PDAC)
In our patient cohort (Table 1), we observed a significant upregulation of VDR (mean 3.7-fold) as well as of CYP24A1 (mean 30.78-fold) mRNA expression in PDAC compared with adjacent parts of the pancreas. mRNA expression of the CaSR decreased in the tumors of most patients by 50%, however did not reach statistical significance (Fig. 1A). CYP27B1 levels did not change (data not shown). Our data are consistent with the microarray gene expression data published in the GEO database by Zhang et al. [28] (Fig. 1B), suggesting that our patient cohort was representative, despite the low sample size.


PDF is attached at the bottom of this page

See also VitaminDWiki

derived from Grassroots 2013
Genetics category listing in VitaminDWiki contains the following

206 articles in Genetics the category

 

see also 183 articles in Vitamin D Receptor, 77 articles in Vitamin D Binding Protein

Vitamin D blood test misses a lot
Blood Test Misses a lot (VDW 3439)

  • Snapshot of the literature by VitaminDWiki - (subject to many future developments)
  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, andi in 2017 is speculated to be 90%
  • Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells appears feasible (personal communication)
    However test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
       especially if it is one of 37+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
    3) Vitamin D Receptor test (<$30) scores are poor
    4) Back Pain
        probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
          The founder of VitaminDWiki took action with clues #3&4

Additional information on the Genes in VitaminDWiki

Gene# of pages
Oct 2017
Location
CPY27A1223 Liver
CYP2R1 626Tissue
Vitamin D Binding Protein 3,450 Blood
CYP27B1803Kidney & Tissue
Vitamin D Receptor 6,030Cell Tissue
CYP24A1 745 excrete excess

See also web

Image

Attached files

ID Name Comment Uploaded Size Downloads
4216 PC-incidence-world-map1.png admin 31 Jul, 2014 13:58 27.32 Kb 6677
4215 Pancreatic Cancer F1.jpg admin 31 Jul, 2014 12:56 37.96 Kb 1969
4214 pancreatic diseases.pdf PDF 2014 admin 31 Jul, 2014 12:56 1.37 Mb 987
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