Xu D, Gruber A, Peterson C, Pisa P
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Leukemia. 1996 Aug;10(8):1354-7.
The human promyelocytic leukemic HL60 cells are immortal and as such express high levels of telomerase activity. All-trans retinoic acid (ATRA) and 1 alpha, 25 dihydroxyvitamin D3 (VD3) induce differentiation of HL60 cells into CD11b+ mature granulocytes and monocytes, respectively. We studied telomerase activity after differentiation of HL60 cells. A marked inhibition of the enzyme activity was observed in the differentiated CD11b+ cells after 72-120 h treatment with either differentiating agent. In contrast, the VD3-treated CD11b- HL60 cells, which failed to undergo differentiation and human erythroleukemic cell line K562, exposed to ATRA retained high levels of telomerase activity. This finding suggests, that telomerase activity is repressed as a differentiation-associated event in HL60 cells. Our results provide the first evidence that immortal leukemic cells, like normal human cells, have a telomerase repressing mechanism which can be activated by differentiation and thus lead to the suppression of telomerase activity. This in vitro model may be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.
人早幼粒细胞白血病HL60细胞是永生的，因此表达高水平的端粒酶活性。全反式维甲酸（ATRA）和1α,25-二羟基维生素D3（VD3）分别诱导HL60细胞分化为CD11b+成熟粒细胞和单核细胞。我们研究了HL60细胞分化后的端粒酶活性。在用任一种分化剂处理72-120小时后，在分化的CD11b+细胞中观察到该酶活性的显著抑制。相反，未发生分化的经VD3处理的CD11b- HL60细胞以及暴露于ATRA的人红白血病细胞系K562保留了高水平的端粒酶活性。这一发现表明，在HL60细胞中，端粒酶活性作为一种与分化相关的事件受到抑制。我们的结果提供了首个证据，即永生白血病细胞与正常人细胞一样，具有一种端粒酶抑制机制，该机制可被分化激活，从而导致端粒酶活性的抑制。这个体外模型可能有助于研究控制端粒酶活性的机制以及寻找生理性端粒酶调节剂。
