Impaired nuclear localization of vitamin D receptor in leukemia cells resistant to calcitriol-induced differentiation.
Calcitriol, the hormonal form of vitamin D(3), induces differentiation of monocytic leukemia cell lines in vitro, without inducing cytotoxicity of the cells. Besides this broad in vitro activity, a clinical implementation of calcitriol, or its analogs, as agents for differentiation therapy has been unsuccessful until now. A better understanding of cellular activities of calcitriol necessary for completion of cell differentiation program could help find better solutions for differentiation therapy of myeloid leukemias. In this paper we describe work carried on subline of acute monocytic leukemia, THP-1 resistant to calcitriol induced differentiation. This resistance correlates with impaired nuclear localization of vitamin D receptor, but not with its total expression in the cells. It also correlates with the resistance to calcitriol-induced growth inhibition, and to phorbol myristate acetate (PMA)-induced cell differentiation.
Humeniuk-Polaczek
Rita
R
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolf Weigl St. 12, Wrocław, Poland.
Marcinkowska
Ewa
E
D021581:Active Transport, Cell Nucleus; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000473:pathology; D009000:Monocytes / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018167:Receptors, Calcitriol; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate