Mano Y, Shimizu T, Tanuma S, Takeda K
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Anticancer Res. 2000 May-Jun;20(3A):1649-52.
Telomerase, the enzyme that synthesizes telomeric DNA, is repressed in normal human somatic cells but is activated with in vitro immortalization or during tumorigenesis. In this study, we investigated telomerase activity and expression of genes involved in telomerase activity in human myeloblastic leukemia ML-1 cells, differentiated synergistically by treatment with all-trans retinoic acid (ATRA) and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF alone was not effective in changing telomerase activity whilst ATRA alone slightly decreased the activity. A combination of ATRA and GM-CSF remarkably reduced telomerase activity. We also detected remarkable suppression of hTERT mRNA expression in ML-1 cells treated with ATRA and GM-CSF. These results indicate that a synergistic down-regulation of telomerase activity and hTERT mRNA expression is induced by treatment with ATRA and GM-CSF in ML-1 cells.
端粒酶是一种合成端粒DNA的酶，在正常人体体细胞中受到抑制，但在体外永生化或肿瘤发生过程中被激活。在本研究中，我们调查了人髓性白血病ML-1细胞中的端粒酶活性以及参与端粒酶活性的基因表达，这些细胞通过全反式维甲酸（ATRA）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）协同处理而分化。单独使用GM-CSF对改变端粒酶活性无效，而单独使用ATRA则使活性略有降低。ATRA和GM-CSF联合使用可显著降低端粒酶活性。我们还检测到用ATRA和GM-CSF处理的ML-1细胞中hTERT mRNA表达受到显著抑制。这些结果表明，ATRA和GM-CSF处理可诱导ML-1细胞中端粒酶活性和hTERT mRNA表达的协同下调。
