Presence of a functional vitamin D receptor does not correlate with vitamin D3 phenotypic effects in myeloid differentiation

Alexis Grande, Rossella Manfredini, Michela Pizzanelli, Enrico Tagliafico, Raffaella Balestri, Francesca Trevisan, Daniela Barbieri, Claudio Franceschi, Renata Battini, Stefano Ferrari, Sergio Ferrari

Research output: Contribution to journalArticle

Abstract

Although VDR is expressed in all the acute myeloid leukemia cell populations studied, most of these leukemias do not exibit any phenotypic response when exposed to VD. To determine whether VD resistance is related to an altered VDR function, we performed an analysis of VDR expression, phosphorylation, DNA binding capacity and transactivation activity in several leukemic myeloid cell lines arrested at different levels of maturation. Our results indicate that VD induces a clear phenotypic effect, i.e. terminal monocytic differentiation, only in leukemic cells of M2/M3 (intermediate myeloblasts) and M5 (monoblasts) types but not in erythroid precursor cells, early leukemic myeloblasts (M0/M1 type) and promyelocytes (M3 type). VDR expression and function are evident in all the nuclear extracts obtained from the different myeloid cell lines after 12 h of VD treatment, but VD activation of monocytic differentiation is limited to a narrow differentiation window characterized by the M2 type myeloid cellular context.

Original languageEnglish
Pages (from-to)497-505
Number of pages9
JournalCell Death and Differentiation
Volume4
Issue number6
Publication statusPublished - 1997

Keywords

  • 1,25 dihydroxyvitamin D3
  • Acute Myeloid Leukemia
  • DNA binding proteins
  • Monocytic differentiation
  • Transcriptional factors
  • Vitamin D receptor

ASJC Scopus subject areas

  • Cell Biology

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    Grande, A., Manfredini, R., Pizzanelli, M., Tagliafico, E., Balestri, R., Trevisan, F., Barbieri, D., Franceschi, C., Battini, R., Ferrari, S., & Ferrari, S. (1997). Presence of a functional vitamin D receptor does not correlate with vitamin D3 phenotypic effects in myeloid differentiation. Cell Death and Differentiation, 4(6), 497-505.