論文

査読有り
2006年10月

Granulocyte macrophage colony-stimulating factor enhances retinoic acid-induced gene expression

JOURNAL OF LEUKOCYTE BIOLOGY
  • Takahisa Shimizu
  • ,
  • Lisa Esaki
  • ,
  • Hiroko Mizuno
  • ,
  • Ken Takeda

80
4
開始ページ
889
終了ページ
896
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1189/jlb.0905502
出版者・発行元
FEDERATION AMER SOC EXP BIOL

We reported previously that treatment of human myeloblastic leukemia ML-1 cells with all-trans retinoic acid (ATRA) in combination with GM-CSF enhances the granulocytic differentiation, which is induced only slightly by ATRA alone. To investigate the mechanism underlying this differentiation and the synergistic effect of ATRA and GM-CSF, we used cDNA microarray to examine gene expression profiles of ML-1 cells treated with ATRA and/or GM-CSF. We identified 22 up-regulated genes in ML-1 cells treated with both reagents and examined the expression of these genes in cells treated with ATRA and/or GM-CSF by Northen blot analysis. Comparison of cells treated with both reagents and cells treated with ATRA or GM-CSF alone revealed that expression of nine of the 19 genes was induced synergistically by combined treatment with ATRA and GM-CSF. Expression of most of these genes was increased only slightly by ATRA alone, and this induction was enhanced by the addition of GM-CSF. These results indicate that GM-CSF enhances ATRA-induced gene expression. Moreover, studies with inhibitors of signaling molecules suggested that activation of JAK2 is associated with the synergistic induction of several genes by ATRA and GM-CSF. JAK2 inhibitor suppressed induction of NBT-reducing activity in ML-1 cells treated with both reagents. It is likely that the enhancer effect of GM-CSF on ATRA-induced gene expression leads to the differentiation induced synergistically by ATRA combined with GM-CSF. Further studies of the mechanism underlying this effect may identify better approaches for the treatment of RA-insensitive leukemia.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1189/jlb.0905502
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000243016000029&DestApp=WOS_CPL

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