All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells.

All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells.
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发表时间:
2000-07
影响因子:
2
通讯作者:
J. Liu;Lee-Jae Guo;Yang Luo;Jun-wei Li;H. Li
J. Liu;Lee-Jae Guo;Yang Luo;Jun-wei Li;H. Li
中科院分区:
医学4区
文献类型:
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作者:
J. Liu;Lee-Jae Guo;Yang Luo;Jun-wei Li;H. Li

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白血病抑制因子(LIF)在人髓母细胞瘤中表达增高。LIF表达或生物学功能的阻断可以抑制髓母细胞瘤细胞(Med-3)的体外生长并诱导分化样表型,这表明当内在去分化因子被抑制或外部分化元件被施加时,Med-3细胞具有再分化潜力。全反式维甲酸(RA)可诱导某些类型的癌症分化,但其对髓母细胞瘤细胞的影响尚未被描述。为了解决上述问题,我们用3个剂量(5、8和10 μ mol/L)的RA处理Med-3细胞,并通过多种方法评价其对靶细胞的作用。结果发现,除了诱导形态学改变和生长抑制,RA可以抑制LIF的表达,以及与时间和剂量相关的方式的Med-3细胞的端粒酶活性。因此,我们的数据表明,RA对Med-3细胞的生长抑制作用可能与LIF下调有关。RA降低端粒酶活性表明,这种酶活性是髓母细胞瘤细胞的潜在分化指标。
Leukemia inhibitory factor (LIF) is prevalently expressed in human medulloblastomas in vivo and in vitro. Blockage of LIF expression or biological function can inhibit in vitro growth and induce differentiation-like phenotypes of medulloblastoma cells (Med-3), suggesting a redifferentiation potential of Med-3 cells when intrinsic dedifferentiation factor(s) is suppressed or external differentiation element(s) is exerted. All-trans retinoic acid (RA) can induce differentiation in some types of cancers but its effect on medulloblastoma cells has not yet been described. To address the above issues, three dosages (5, 8 and 10 mumol/L) of RA were used to treat Med-3 cells and their effects on the target cells were evaluated by multiple approaches. It was found that, in addition to induction of morphological changes and growth inhibition, RA could repress LIF expression as well as the telomerase activity of Med-3 cells in time- and dose-related fashions. Our data thus suggest that the growth inhibitory effect of RA on Med-3 cells may be correlated with the LIF down-regulation. Reduction of telomerase activity by RA indicates that this enzymatic activity is a potential differentiation indicator of medulloblastoma cells.