Hsu C Y, Yung B Y
Graduate Institute of Pharmacology, National Yang Ming University, Taiwan, Republic of China.
Oncogene. 1998 Feb 19;16(7):915-23. doi: 10.1038/sj.onc.1201615.
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.
人早幼粒细胞白血病HL - 60细胞用视黄酸（RA，10微摩尔，处理1 - 5天）诱导进行粒细胞分化。在RA诱导的分化过程中，核磷蛋白/B23 mRNA的稳态水平下降。在RA诱导的分化过程中，细胞内核磷蛋白/B23总蛋白水平也下降。稳定性和核转录分析表明，RA处理的HL - 60细胞中核磷蛋白/B23 mRNA的减少是由转录调控的。与c - myc mRNA不同，在血清饥饿导致的生长停滞期间，核磷蛋白/B23 mRNA几乎没有下降。因此，视黄酸处理后HL - 60细胞中核磷蛋白/B23 mRNA表达的减少可归因于细胞分化，而非RA诱导的生长停滞。核磷蛋白/B23反义寡聚物处理显著增强了RA诱导的细胞分化。本研究结果表明，核磷蛋白/B23是细胞分化过程中核仁功能下调的关键因素之一。
