Vitamin D receptor and calcium sensing receptor polymorphisms and colorectal cancer survival in Newfoundland population

BackgroundTo explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).Materials and methodsForty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (n=3) or from euthyroid patients without PHPT during thyroid surgery (n=7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR.ResultsImmunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, bothVDRandCASRmRNAs were reduced by 0.36- and 0.45-fold change (P<0.001) andCD1andPTHmRNAs were increased by 9.4- and 17.4-fold change respectively (P<0.001) in adenomatous parathyroid tissue.PTHmRNA correlated with plasma PTH (r=0.864;P<0.001), but not with adenoma weight, whileCD1mRNA correlated with adenoma weight (r=0.715;P<0.001). There were no correlations betweenVDRandCASRmRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases inVDRandCASRmRNA expressions and the increases inPTHandCD1mRNA expressions.ConclusionsThe expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition,CD1expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.

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Vitamin D receptor, a tumor suppressor in skin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0367 ◽

2015 ◽

Vol 93 (5) ◽

pp. 349-354 ◽

Cited By ~ 21

Author(s):

Daniel D. Bikle

Keyword(s):

Vitamin D ◽

Tumor Suppressor ◽

Vitamin D Receptor ◽

Tumor Formation ◽

Calcium Sensing Receptor ◽

Keratinocyte Proliferation ◽

Calcium Sensing ◽

Damage Repair ◽

Proliferation And Differentiation ◽

Active Investigation

Vitamin D and calcium are well-established regulators of keratinocyte proliferation and differentiation. Therefore, it was not a great surprise that deletion of the vitamin D receptor (VDR) should predispose the skin to tumor formation, and that the combination of deleting both the VDR and calcium sensing receptor (CaSR) should be especially pro-oncogenic. In this review I have examined 4 mechanisms that appear to underlie the means by which VDR acts as a tumor suppressor in skin. First, DNA damage repair is curtailed in the absence of the VDR, allowing mutations in DNA to accumulate. Second and third involve the increased activation of the hedgehog and β-catenin pathways in the epidermis in the absence of the VDR, leading to poorly regulated proliferation with reduced differentiation. Finally, VDR deletion leads to a shift in the expression of long noncoding RNAs toward a more oncogenic profile. How these different mechanisms interact and their relative importance in the predisposition of the VDR null epidermis to tumor formation remain under active investigation.

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Associations of Vitamin D Receptor, Calcium-Sensing Receptor and Parathyroid Hormone Gene Polymorphisms with Calcium Homeostasis and Peripheral Bone Density in Adult Finns

Journal of Nutrigenetics and Nutrigenomics ◽

10.1159/000204960 ◽

2009 ◽

Vol 2 (2) ◽

pp. 55-63 ◽

Cited By ~ 17

Author(s):

M.M.L. Laaksonen ◽

T.A. Outila ◽

M.U.M. Kärkkäinen ◽

V.E. Kemi ◽

H.J. Rita ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Bone Density ◽

Vitamin D Receptor ◽

Calcium Homeostasis ◽

Gene Polymorphisms ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

Peripheral Bone

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Investigation of effect of vitamin D receptor, calcium-sensing receptor and β-catenin on cutaneous squamous cell carcinoma

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0434 ◽

2020 ◽

Vol 45 (1) ◽

pp. 91-98

Author(s):

Berrin Tuğrul ◽

Sevinç Söylev ◽

Peyker Temiz ◽

Gülsüm Gençoğlan

Keyword(s):

Vitamin D ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Vitamin D Receptor ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Beta Catenin ◽

Calcium Sensing Receptor ◽

Tissue Samples ◽

Calcium Sensing

AbstractBackgroundCutaneous squamous cell carcinoma (cSCC) is a malignant and invasive tumor which is originated from epidermis with a high incidence among non-melanoma skin cancers. The aim of this study was to determine whether vitamin D receptor (VDR), calcium-sensing receptor (CaSR) and beta catenin (β-catenin) proteins have an effect on cSCC.Materials and methodsVDR, CaSR and β-catenin proteins in tissue samples of cSCC and control group were analyzed by immunohistochemistry (IHC) and Western blotting (WB) method. IHC findings were statistically evaluated.ResultsIHC staining density of VDR and β-catenin were higher in cSCC tissue samples than control. The difference between IHC staining density of VDR and β-catenin in the patient and the control groups were statistically significant (p = 0.021, p = 0.021, respectively), but not for CaSR (p = 0.237). While the VDR and β-catenin staining rates obtained by the IHC method could be supported by WB results, the WB bands for CaSR could not be shown.ConclusionThe findings suggest that VDR and β-catenin may have an effect on the disease. Further research is required to better understand the role of VDR and β-catenin together on cSCC.

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