ArticleLaboratory investigation; a journal of technical methods and pathology2014
Role of local bioactivation of vitamin D by CYP27A1 and CYP2R1 in the control of cell growth in normal endometrium and endometrial carcinoma.
Article in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Vitamin D and Endometrium: A Systematic Review of a Neglected Area of Research.International journal of molecular sciences · 2018Pooled it
- Trial
- Exploring Vitamin D Metabolism in Gynaecological Malignancies: Redox-Dependent and Redox-Independent Anticancer Mechanisms From Preclinical Models to Clinical Evidence.Cancer medicine · 2026Review
- Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025Review
- NOVA2 expression in pituitary gland and in functioning and non-functioning pituitary adenomas: a preliminary study.Acta neurochirurgica · 2025Article
- Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome.International journal of molecular sciences · 2025Review
- Vitamin D, immune microenvironment, and cervical lesions: mechanisms and therapeutic strategies from polyps to carcinoma.Frontiers in nutrition · 2025Review
- Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.Frontiers in genetics · 2025Review
- [Resolution of the national interdisciplinary council of experts "High-dose vitamin D (Devilam) in the practice of an obstetrician-gynecologist"].Problemy endokrinologii · 2024Article
- Vitamins in Gynecologic Malignancies.Nutrients · 2024Review
- Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.Reproductive health · 2024Review
- Vitamin D and Mitosis Evaluation in Endometriosis: A Step toward Discovering the Connection?Biomedicines · 2023Article
- Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone.International journal of molecular sciences · 2022Article
- Association between gestational trophoblastic disease (GTD) history and clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.Reproductive biology and endocrinology : RB&E · 2022Article
- Phosphate, Calcium, and Vitamin D: Key Regulators of Fetal and Placental Development in Mammals.Advances in experimental medicine and biology · 2022Review
- New Variants of the Cytochrome P450 2R1 (Biomolecules · 2021Article
- Non-classical Vitamin D Actions for Renal Protection.Frontiers in medicine · 2021Review
- Review
- Characterization of VDR and CYP27B1 expression in the endometrium during the menstrual cycle before embryo transfer: implications for endometrial receptivity.Reproductive biology and endocrinology : RB&E · 2020Article
- The factors associated with Vitamin D deficiency in community dwelling elderly in Korea.Nutrition research and practice · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin D (VD) deficiency has been suggested as a risk factor for cancer. One recognized mechanism is that the low-serum 25-hydroxyvitamin D (25(OH)D) of VD deficiency reduces intratumoral 25(OH)D conversion to 1α,25-dihydroxyvitamin D (1,25D, the hormonal form of VD), compromising 1,25D-VD receptor (VDR) antitumoral actions. Reduced tumoral VDR and increased CYP24A1, the enzyme that degrades 1,25D and 25(OH)D, further worsen cancer progression. Importantly, in cells expressing CYP27A1 and/or CYP2R1, which convert inert VD into 25(OH)D, low-serum VD may reduce intratumoral 25(OH)D synthesis thereby compromising VDR antitumoral actions because 25(OH)D can activate the VDR directly and enhance 1,25D-VDR action. Therefore, this study examined whether abnormal endometrial expression of CYP27A1 and/or CYP2R1 may impair VDR-antiproliferative properties in endometrial carcinoma (EC). Immunohistochemical analysis of tissue microarrays of normal human endometrium (NE; n=60) and EC (n=157) showed the expected lower VDR expression in EC (P=0.0002). Instead, CYP24A1 expression was lower in EC compared with NE, while CYP27A1 and CYP2R1 expressions were higher (P=0.0002; P=0.03). Furthermore, in NE and EC, CYP2R1 and CYP27A1 expression correlated directly with nuclear VDR levels, an indicator of ligand-induced VDR activation, and inversely with the proliferation marker Ki67. Accordingly, in the endometrioid carcinoma cell lines IK, RL95/2 and HEC1-A, which express VDR, CYP27A1, and CYP2R1, VD efficaciously reduced cell viability and colony number, with a time course that paralleled actual increases in both intracellular 25(OH)D and nuclear VDR levels. Thus, VD may protect from EC progression in part through increased intratumoral 25(OH)D production by CYP27A1 and CYP2R1 for autocrine/paracrine enhancement of 1,25D-VDR-antiproliferative actions.
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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.