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-delta.

Abstract

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.

• Authors: Akira Uruno, Naoya Noguchi, Ken Matsuda, Koji Nata, Takeo Yoshikawa, Youichiro Chikamatsu, Hiroyuki Kagechika, Hideo Harigae, Sadayoshi Ito, Hiroshi Okamoto, Akira Sugawara
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 90 Issue 2 Pg. 235-47 (Aug 2011) ISSN: 1938-3673 [Electronic] England
• PMID: 21393419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Retinoids
• Tetrahydronaphthalenes
• tamibarotene
• Tretinoin
• Protein Kinase C-delta
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (genetics)
• Benzoates (pharmacology)
• Cell Adhesion (drug effects)
• Endothelial Cells (cytology)
• Gene Expression Regulation, Neoplastic (drug effects)
• HL-60 Cells
• Humans
• Leukemia (pathology)
• Protein Kinase C-delta (drug effects, genetics)
• Retinoids (pharmacology)
• Tetrahydronaphthalenes (pharmacology)
• Tretinoin (pharmacology)