ArticleCancer research2012
A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis.British journal of cancer · 2017Pooled it
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- Serum 25 (OH) D levels and risk of female-specific cancer in premenopausal women: a prospective study.Frontiers in nutrition · 2025Article
- Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage.Journal of molecular cell biology · 2024Article
- Better survival was found in patients treated with breast-conserving surgery compared with mastectomy in malignant phyllodes tumor of the breast.Updates in surgery · 2024Article
- PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.Frontiers in endocrinology · 2022Review
- Omics Technologies to Decipher Regulatory Networks in Granulocytic Cell Differentiation.Biomolecules · 2021Article
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- Vitamin D regulation of HAS2, hyaluronan synthesis and metabolism in triple negative breast cancer cells.The Journal of steroid biochemistry and molecular biology · 2020Article
- Article
- 1α,25(OH)Frontiers in pharmacology · 2020Article
- Exploring vitamin D metabolism and function in cancer.Experimental & molecular medicine · 2018Review
- The impact of VDR expression and regulation in vivo.The Journal of steroid biochemistry and molecular biology · 2018Article
- Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin EKidney research and clinical practice · 2017Article
- Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications.Oncotarget · 2017Review
- 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.PloS one · 2016Article
- Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.Seminars in cancer biology · 2015Review
- Gene Signatures of 1,25-Dihydroxyvitamin D3 Exposure in Normal and Transformed Mammary Cells.Journal of cellular biochemistry · 2015Article
- Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells.Cancer genetics · 2015Article
- TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis via modulation of DNA damage/repair system.Carcinogenesis · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Both epidemiologic and laboratory studies have shown the chemopreventive effects of 1α,25-dihydroxyvitamin D(3) (1,25-VD) in tumorigenesis. However, understanding of the molecular mechanism by which 1,25-VD prevents tumorigenesis remains incomplete. In this study, we used an established mouse model of chemical carcinogenesis to investigate how 1,25-VD prevents malignant transformation. In this model, 1,25-VD promoted expression of the DNA repair genes RAD50 and ATM, both of which are critical for mediating the signaling responses to DNA damage. Correspondingly, 1,25-VD protected cells from genotoxic stress and growth inhibition by promoting double-strand break DNA repair. Depletion of the vitamin D receptor (VDR) reduced these genoprotective effects and drove malignant transformation that could not be prevented by 1,25-VD, defining an essential role for VDR in mediating the anticancer effects of 1,25-VD. Notably, genotoxic stress activated ATM and VDR through phosphorylation of VDR. Mutations in VDR at putative ATM phosphorylation sites impaired the ability of ATM to enhance VDR transactivation activity, diminishing 1,25-VD-mediated induction of ATM and RAD50 expression. Together, our findings identify a novel vitamin D-mediated chemopreventive mechanism involving a positive feedback loop between the DNA repair proteins ATM and VDR.
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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.