Side-chain modified vitamin D analogs induce rapid accumulation of VDR in the cell nuclei proportionately to their differentiation-inducing potential

• Published in: Steroids Vol. 73; no. 14; pp. 1359 - 1366
• Main Authors: Gocek, Elżbieta, Kiełbiński, Marek, Wyłób, Paulina, Kutner, Andrzej, Marcinkowska, Ewa
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 22.12.2008; Elsevier
• Subjects: Acute myeloid leukemia; Biological and medical sciences; Blotting, Western; Cell Differentiation - drug effects; Cell Nucleus - metabolism; Differentiation; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; HL-60 Cells - drug effects; HL-60 Cells - pathology; Humans; Intracellular localization; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Medical sciences; Polymerase Chain Reaction; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Side-chain modified analogs; VDR; Vertebrates: endocrinology; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; AML; PBS; 1,25D; Side-chain modified analogs; VDR; HRP; VDRE; MCF; VDA; Vitamin D; FCS; Intracellular localization; Differentiation; Acute myeloid leukemia; Acute myelogenous leukemia; Malignant hemopathy; Micronutrient; Analog; Intracellular; Localization; Cancer
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2008.06.010

1,25-Dihydroxyvitamin D 3 (1,25D) regulates gene transcription through a nuclear vitamin D receptor (VDR) which acts as a ligand-regulated transcription factor. Some structural vitamin D analogs (VDAs) are selective in their biological actions, because they retain cell-differentiating potential, while their calcemic activity is reduced. In this article we have shown that in untreated HL60 cells the expression level of VDR is low, in spite of constant presence of VDR mRNA. Furthermore we have shown that one of the most rapid effects of either 1,25D or VDAs is nuclear accumulation of VDR, which is proportional to the differentiation-inducing potential of given analog. We observed this effect not only in HL60 cells, but also in blast cells isolated from patients with acute myeloid leukemias. After longer incubation time of the cells with various VDAs, the expression levels of VDR have become unrelated to the final differentiation effect.