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Vitamin D receptor (VDR) and metabolizing enzymes CYP27B1 and CYP24A1 in breast cancer. 2020

Ioannis A Voutsadakis
Algoma District Cancer Program, Sault Area Hospital, 750 Great Northern Road, Sault Ste. Marie, ON, P6B 0A8, Canada. ivoutsadakis@yahoo.com.

Vitamin D Receptor (VDR), a nuclear steroid receptor, is a transcription factor with a primary physiologic role in calcium metabolism. It has also a physiologic role in breast tissues during development of the gland and postpartum. In addition, it is commonly expressed in breast cancer and has tumor suppressive effects. Cytochrome enzymes CYP27B1 and CYP24A1 that perform the final conversion of the circulating form of vitamin D, 25-hydroxyvitamin D (25-OHD) to the active VDR ligand, 1a,25-dihydroxyvitamin D and the catabolism of it to inactive 24,25-dihydroxyvitamin D, respectively, are also expressed in breast cancer tissues. Defective regulation of the receptor and the metabolic enzymes of VDR ligand is prevalent in breast cancer and leads to decreased VDR signaling. The expression and molecular defects of VDR, CYP27B1 and CYP24A1 that perturb physiologic function, the implications for breast cancer progression and therapeutic opportunities are discussed in this paper.

UI MeSH Term Description Entries
D001940 Breast In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES. Breasts
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014807 Vitamin D A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
D015090 25-Hydroxyvitamin D3 1-alpha-Hydroxylase A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol). 25-Hydroxycholecalciferol 1-Hydroxylase,CYP27B1,Calcidiol 1-Monooxygenase,Cytochrome P-450 CYP27B1,25-Hydroxycholecalciferol-1-Hydroxylase,25-Hydroxyergocalciferol 1-alpha-Hydroxylase,25-Hydroxyvitamin D 1-alpha-Hydroxylase,25-Hydroxyvitamin D(3) 1 alpha-Hydroxylase,25-Hydroxyvitamin D2 1-hydroxylase,1-alpha-Hydroxylase, 25-Hydroxyergocalciferol,1-alpha-Hydroxylase, 25-Hydroxyvitamin D,1-hydroxylase, 25-Hydroxyvitamin D2,25 Hydroxycholecalciferol 1 Hydroxylase,25 Hydroxyergocalciferol 1 alpha Hydroxylase,25 Hydroxyvitamin D 1 alpha Hydroxylase,25 Hydroxyvitamin D2 1 hydroxylase,25 Hydroxyvitamin D3 1 alpha Hydroxylase,Calcidiol 1 Monooxygenase,Cytochrome P 450 CYP27B1
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D018167 Receptors, Calcitriol Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors. Calcitriol Receptors,Cholecalciferol Receptors,Receptors, Vitamin D,Vitamin D 3 Receptors,Vitamin D Receptors,1,25-Dihydroxycholecalciferol Receptor,1,25-Dihydroxycholecalciferol Receptors,1,25-Dihydroxyvitamin D 3 Receptor,1,25-Dihydroxyvitamin D3 Receptor,1,25-Dihydroxyvitamin D3 Receptors,Calcitriol Receptor,Receptors, 1,25-Dihydroxyvitamin D 3,Receptors, Cholecalciferol,Receptors, Vitamin D 3,Receptors, Vitamin D3,Vitamin D 3 Receptor,Vitamin D Receptor,Vitamin D3 Receptor,Vitamin D3 Receptors,1,25 Dihydroxycholecalciferol Receptor,1,25 Dihydroxycholecalciferol Receptors,1,25 Dihydroxyvitamin D 3 Receptor,1,25 Dihydroxyvitamin D3 Receptor,1,25 Dihydroxyvitamin D3 Receptors,D Receptor, Vitamin,D Receptors, Vitamin,D3 Receptor, 1,25-Dihydroxyvitamin,D3 Receptor, Vitamin,D3 Receptors, 1,25-Dihydroxyvitamin,D3 Receptors, Vitamin,Receptor, 1,25-Dihydroxycholecalciferol,Receptor, 1,25-Dihydroxyvitamin D3,Receptor, Calcitriol,Receptor, Vitamin D,Receptor, Vitamin D3,Receptors, 1,25-Dihydroxycholecalciferol,Receptors, 1,25-Dihydroxyvitamin D3

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