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

     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.

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See also VitaminDWiki

• Pancreatic Cancer protects itself deactivating HNF4A (which can be reactivated by the Vitamin D Receptor) – April 2024
• Pancreatic cancer risk of death reduced 19 percent by Vitamin D – meta-analysis June 2017
• Restoring vitamin D levels to Pancreatic patients required up to 20000 IU daily – May 2012
  20,000 IU is needed to restore vitamin D in the blood stream, perhaps need far more to TREAT Pancreatic Cancer
• Prostate cancer reduced in high vitamin D two studies – April 2012 one trial used 40,000 IU daily
• VERY LARGE doses of vitamin D have CURED 2,000 people of MS in Brazil perhaps large doses are needed for Pancreatic Cancer as well.
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• Role of Vitamin D in human Diseases and Disorders – An Overview – DBP, VDR June 2014
• Notice: A LOT of vitamin D is need to PREVENT Pancreatic Cancer

Genetics category listing in VitaminDWiki contains the following

343 articles in the Genetics category

see also

• Vitamin D Receptor has 530 items
• Vitamin D Binding Protein = GC has 178 items
• CYP27B1 has 63 items
• CYP24A1 in title of 39+ items
• CYP2R1 25+ items
• Calcidiol has 48 items
• Calcitriol has 62 items
• Topical Vitamin D
• Nanoemulsion Vitamin D may be a substantially better form
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• CYP3A4 (7 as of Dec 2022)
• Getting Vitamin D into your body
• 

Vitamin D blood test misses a lot

• Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
• Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
• A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
  • 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 51+ diseases related to Vitamin D Receptor
  2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
  3) DNA and VDR tests - 100 to 200 dollars $100 to $250
  4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
     Genes are good, have enough Magnesium, etc.
  5) 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&5

See also web

• study on this page was cited 40 times as of Sept 2021
• 1.5 % is US will be diagnosed with pancreatic cancer at some point during their lifetime
• Pancreatic Cancer projected to be the 2nd leading cause of Cancer deaths by 2030 PubMed May 2014
• Pancreatic Cancer statistics and charts Pancreatic Cancer Action UK,
  Notice that the map shows Pancreatic Cancer, like many other Cancers, is strongly related to latitude (UVB)