ArticleThyroid : official journal of the American Thyroid Association2010
Thyroid cancer resistance to vitamin D receptor activation is associated with 24-hydroxylase levels but not the ff FokI polymorphism.
Article in Thyroid : official journal of the American Thyroid Association, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Vitamin D-Related Genes and Thyroid Cancer-A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Serum 25-Hydroxyvitamin D Is Inversely Associated with Nasopharyngeal Carcinoma: A Hospital-Based Matched Case-Control Study in Malaysia.Nutrients · 2024Article
- Review
- 1,25‑Dihydroxyvitamin D3 enhances the susceptibility of anaplastic thyroid cancer cells to adriamycin‑induced apoptosis by increasing the generation of reactive oxygen species.Molecular medicine reports · 2019Article
- Vitamin D receptor and progesterone receptor protein and gene expression in papillary thyroid carcinomas: associations with histological features.Journal of endocrinological investigation · 2017Article
- Article
- Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.Journal of endocrinological investigation · 2015Article
- Review
- Insights into genetic and epigenetic determinants with impact on vitamin d signaling and cancer association studies: the case of thyroid cancer.Frontiers in oncology · 2014Review
- Very important pharmacogene summary for VDR.Pharmacogenetics and genomics · 2012Review
- Impaired vitamin D activation and association with CYP24A1 haplotypes in differentiated thyroid carcinoma.Thyroid : official journal of the American Thyroid Association · 2012Article
- Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012Article
- Gene expression of vitamin D metabolic enzymes at baseline and in response to vitamin D treatment in thyroid cancer cell lines.Oncology · 2012Article
- Vitamin D, Thyroid Autoimmunity and Cancer: An Interplay of Different Factors.Indian journal of endocrinology and metabolismReview
- Vitamin D Status and VDR Polymorphisms as Prognostic Factors in Differentiated Thyroid Carcinoma.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006.
methodsThyroid cancer cell lines were analyzed for VDR and RXR protein by Western blot. Cell growth after VDR agonist treatment (calcitriol or DP006) was assessed after 6 days of treatment by viable cell assay. To investigate calcitriol/DP006 resistance in VDR-expressing cells, the VDR was sequenced and 1-α and 24-hydroxylase mRNA expression was assessed.
resultsVDR protein was variably expressed in the thyroid cancer cell lines and its presence was not sufficient for decreased viable cell count in response to calcitriol or DP006. The most sensitive cells (TPC1) have an ff FokI VDR polymorphism and the most resistant cells (HTh7 and 8505C) have an FF FokI VDR. This is a unique finding given that the balance of the literature of VDR polymorphisms describes an association of the ff FokI polymorphism with cancer risk and/or decreased VDR transactivation. 1-α and 24-hydroxylase mRNA expression before and after VDR agonist therapy was examined. 1-α-Hydroxylase levels did not change after calcitriol treatment. However, we found that higher baseline 24-hydroxylase levels and/or lower stimulation of 24-hydroxylase levels after calcitriol treatment were associated with relative resistance to calcitriol/DP006.
conclusionsThe VDR represents a novel therapeutic target in poorly differentiated thyroid cancer; however, the efficacy of VDR agonist therapy to decrease viable thyroid cancer cell count cannot be predicted solely on the presence of the VDR. The FF FokI VDR genotype and high baseline 24-hydroxylase levels were associated with relative resistance to calcitriol and DP006. Therefore, identifiable markers of sensitivity or resistance to VDR agonist therapy may allow for a personalized use of these agents in poorly differentiated thyroid cancer.
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