Down-regulation of nucleophosmin/B23 during retinoic acid-induced differentiation of human promyelocytic leukemia HL-60 cells.
Human promyelocytic leukemia HL-60 cells were induced to undergo granulocytic differentiation by treatment with retinoic acid (RA, 10 microM, 1-5 days). The steady-state level of nucleophosmin/B23 mRNA decreased during the RA-induced differentiation. There was also decrease in the level of total cellular nucleophosmin/B23 protein during the RA-induced differentiation. Stabilization and nuclear run-on assays indicate that the decrease in nucleophosmin/B23 mRNA in RA-treated HL-60 cells was transcriptionally regulated. Unlike c-myc mRNA, there was virtually no decline of nucleophosmin/B23 mRNA during the growth arrest by serum-starvation. The decrease in nucleophosmin/B23 mRNA expression in HL-60 cells subsequent to retinoic acid treatment can thus be attributed to cellular differentiation rather than the growth arrest induced by RA. Nucleophosmin/B23 antisense oligomer treatment significantly potentiated RA-induced cellular differentiation. Results of this study suggest that nucleophosmin/B23 is one of the key elements in the down-regulation of nucleolar function for cellular differentiation.
Hsu
C Y
CY
Graduate Institute of Pharmacology, National Yang Ming University, Taiwan, Republic of China.
Yung
B Y
BY
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013873:Thionucleotides; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013873:Thionucleotides; D000090243:Nucleophosmin; D014212:Tretinoin