ArticleCancer biology & therapy2010
DNA methylation-related vitamin D receptor insensitivity in breast cancer.
Article in Cancer biology & therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Vitamin D-Related Genes and Thyroid Cancer-A Systematic Review.International journal of molecular sciences · 2022Pooled it
- The expression and methylation status of vitamin D receptor gene in Behcet's disease.Immunity, inflammation and disease · 2019Trial
- Vitamin D receptor gene polymorphisms and prognosis of breast cancer among African-American and Hispanic women.PloS one · 2013Trial
- Synthetic Modulators of the Vitamin D Receptor: From Structural Innovation to Disease-Specific Applications.Biomolecules · 2026Review
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- The Association ofAnalytical cellular pathology (Amsterdam) · 2025Article
- Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.Frontiers in genetics · 2025Review
- The Impact of Vitamin D and Its Dietary Supplementation in Breast Cancer Prevention: An Integrative Review.Nutrients · 2024Review
- Vitamin D in tuberous sclerosis complex-associated tumors.Frontiers in pediatrics · 2024Article
- Methylation of the Vitamin D Receptor Gene in Human Disorders.International journal of molecular sciences · 2023Review
- A Review: Highlighting the Links between Epigenetics, COVID-19 Infection, and Vitamin D.International journal of molecular sciences · 2022Review
- Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease.International journal of molecular sciences · 2022Review
- Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling.International journal of molecular sciences · 2022Review
- Vitamin D and Breast Cancer: Mechanistic Update.JBMR plus · 2021Article
- Article
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma.International journal of medical sciences · 2021Observational
- Policing Cancer: Vitamin D Arrests the Cell Cycle.International journal of molecular sciences · 2020Review
- A novel vitamin D gene therapy for acute myeloid leukemia.Translational oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Calcitriol (1α, 25(OH)(2)-Vitamin D3) binds to the vitamin D receptor (VDR) and regulates differentiation of the normal mammary gland, and may therefore be useful in breast cancer treatment or prevention. Many breast cancer cells are, however, resistant to Calcitriol. In this study, we investigated the resistance mechanism and the role of epigenetic silencing of VDR by promoter hypermethylation. Bisulfite sequencing of the VDR promoter region revealed methylated CpG islands at -700 base pairs (bp) upstream and near the transcription start site. VDR CpG islands were demethylated by 5'deoxy-azacytidine treatment, and this was accompanied by a parallel increase in VDR mRNA levels in breast cancer cell lines. Quantitative methylation-specific PCR analyses confirmed hypermethylation of these CpG islands in primary tumors, and its absence in normal breast tissue. VDR transcripts detected in breast cancers were predominantly 5'-truncated, while normal breast tissue expressed full-length transcripts. Consistent with this observation, genes containing the VDR-responsive element (VDRE), such as cytochrome p450 hydroxylases, p21 or C/EBP were underexpressed in breast cancers compared to normal breast samples. Expression of the active longer transcripts of VDR was restored with 5'deoxy-Azacytidine (AZA) treatment, with a concurrent increase in expression of VDRE-containing genes. Thus, promoter methylation-mediated silencing of expression of the functional variants of VDR may contribute to reduced expression of downstream effectors of the VDR pathway and subsequent Calcitriol insensitivity in breast cancer. These data suggest that pharmacological reversal of VDR methylation may re-establish breast cancer cell susceptibility to differentiation therapy using Calcitriol.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.