All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells

Hideaki Nakajima, Masahiro Kizaki, Hironori Ueno, Akihiro Muto, Nobuyuki Takayama, Hiromichi Matsushita, Akira Sonoda, Yasuo Ikeda

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (D3) are well known for inducing differentiation in many leukemic cell lines. The nuclear signalling pathways of RA and D3 are mediated through their cognate receptors, the retinoic acid receptor (RAR) and vitamin D3 receptor (VDR), respectively. Retinoid X receptor (RXR) is an auxiliary factor that forms a heterodimer with RAR and VDR, enabling their efficient transcriptional activation, 9-cis RA, a high-affinity ligand for RXR, greatly enhanced D3-induced CD14 expression in U937 cells, while RA alone did not induce CD14 expression. 9-cis RA also resulted in morphological changes of U937 cells to macrophage-like cells when combined with D3 while RA alone resulted in granulocyte-like cells. RA and D3 together enhanced c-fms expression, phagocytic activity, and acted synergistically to promote nitroblue tetrazolium reduction activity and inhibit proliferation. Northern analysis showed that U937 cells constitutively expressed RAR-α, VDR and RXR-α mRNAs. RA or D3 alone or in combination did not affect RAR-α and VDR expression, while g-cis RA and 9-cis RA plus all-trans RA significantly reduced RXR-α expression. Interestingly, D3 could restore the down-regulation of RXR-α mRNA by 9-cis RA. These findings suggest that there is crossover of the nuclear signalling pathways of RA and D3 This may have clinical implications in that RA and D3 may be used in combination for differentiation-inducing therapy in acute myelogenous leukemia and myelodysplastic syndrome.

Original languageEnglish
Pages (from-to)665-676
Number of pages12
JournalLeukemia Research
Volume20
Issue number8
DOIs
Publication statusPublished - 1996 Aug

Fingerprint

U937 Cells
Calcitriol
Tretinoin
Retinoid X Receptors
Retinoic Acid Receptors
Calcitriol Receptors
NSC 153174
alitretinoin
Nitroblue Tetrazolium
Messenger RNA
Myelodysplastic Syndromes
Granulocytes
Acute Myeloid Leukemia
Transcriptional Activation
Down-Regulation
Macrophages
Ligands
Cell Line

Keywords

  • 9-cis retinoic acid
  • All-trans retinoic acid
  • Differentiation
  • U937
  • Vitamin D

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Nakajima, H., Kizaki, M., Ueno, H., Muto, A., Takayama, N., Matsushita, H., ... Ikeda, Y. (1996). All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells. Leukemia Research, 20(8), 665-676. https://doi.org/10.1016/0145-2126(96)00020-3

All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells. / Nakajima, Hideaki; Kizaki, Masahiro; Ueno, Hironori; Muto, Akihiro; Takayama, Nobuyuki; Matsushita, Hiromichi; Sonoda, Akira; Ikeda, Yasuo.

In: Leukemia Research, Vol. 20, No. 8, 08.1996, p. 665-676.

Research output: Contribution to journalArticle

Nakajima, H, Kizaki, M, Ueno, H, Muto, A, Takayama, N, Matsushita, H, Sonoda, A & Ikeda, Y 1996, 'All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells', Leukemia Research, vol. 20, no. 8, pp. 665-676. https://doi.org/10.1016/0145-2126(96)00020-3
Nakajima, Hideaki ; Kizaki, Masahiro ; Ueno, Hironori ; Muto, Akihiro ; Takayama, Nobuyuki ; Matsushita, Hiromichi ; Sonoda, Akira ; Ikeda, Yasuo. / All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells. In: Leukemia Research. 1996 ; Vol. 20, No. 8. pp. 665-676.
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