All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-δ

Journal of Leukocyte Biology

Akira Uruno²  Akira Sugawara²  Takeo Yoshikawa²  Youichiro Chikamatsu²  Koji Nata²  Hiroyuki Kagechika¹  Ken Matsuda²  Hiroshi Okamoto and²  Naoya Noguchi²  Sadayoshi Ito²  Hideo Harigae² 

[1]  School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan;Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan;

关键词: retinoic acid receptor;    endothelial cells;    adhesion;   

DOI  :  10.1189/jlb.0109025

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ATRA and a synthetic RAR agonist tamibarotene (Am80) induce granulocytic differentiation of human acute leukemia HL-60 cells and have been used in antineoplastic therapy. ATRA induces CD38 antigen during HL-60 cell differentiation, which interacts with CD31 antigen on the vascular EC surface and may induce disadvantages in the therapy. We here examined the mechanisms of the ATRA-mediated CD38 induction and compared the difference between ATRA- and tamibarotene-mediated induction. Tamibarotene-induced HL-60 cell adhesion to ECs was 38% lower than ATRA, and NB4 cell adhesion to ECs by tamibarotene was equivalent to ATRA, which induced CD38 gene transcription biphasically in HL-60 cells, the early-phase induction via DR-RARE containing intron 1, and the delayed-phase induction via RARE lacking the 5′-flanking region. In contrast to ATRA, tamibarotene induced only the early-phase induction, resulting in its lower CD38 induction than ATRA. A PKCδ inhibitor, rottlerin, and siRNA-mediated PKCδ knockdown suppressed the ATRA-induced CD38 promoter activity of the 5′-flanking region, whereas a RAR antagonist, LE540, or RAR knockdown did not affect it. Cycloheximide and rottlerin suppressed the delayed-phase induction of CD38 expression by ATRA but did not affect the early-phase induction. Moreover, ATRA, but not tamibarotene, induced PKCδ expression without affecting its mRNA stability. The diminished effect of tamibarotene on CD38-mediated HL-60 cell adhesion to ECs compared with ATRA is likely a result of the lack of its delayed-phase induction of CD38 expression, which may be advantageous in antineoplastic therapy.

【 授权许可】

Unknown