p27KIP1 and GATA-1 are potential downstream molecules in activin A-induced differentiation and apoptosis pathways in CML cells.
p27KIP1 and GATA-1 are potential downstream molecules in activin A-induced differentiation and apoptosis pathways in CML cells.
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DOI：
10.3892/or.16.5.1099
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发表时间：
2006-11
期刊：
影响因子：
4.2
通讯作者：
Y. Fukuchi;K. Yamato;Chiharu Kawamura;Y. Ikeda;M. Kizaki
中科院分区：
文献类型：
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作者：
Y. Fukuchi;K. Yamato;Chiharu Kawamura;Y. Ikeda;M. Kizaki
已知p27 KIP 1是人癌细胞中细胞分化和凋亡的调节因子。我们以前曾报道过，人慢性髓性白血病（CML）KU 812和K562细胞对TGF-β超家族成员激活素A的处理表现出细胞增殖抑制。KU 812和K562细胞可分别诱导凋亡和向红系分化。我们在此报道激活素A诱导CML细胞中p27 KIP 1的表达，同时沿着诱导细胞分化和凋亡。人p27 KIP 1基因启动子区存在红系相关转录因子加塔-1的结合序列。加塔-1蛋白在激活素A处理的KU 812和K562细胞中的表达在这两个细胞系中显示出不同的调节。通常观察到p27 KIP 1的诱导，但其不对应于激活素A处理的CML细胞系中的加塔-1的表达水平。此外，在两种类型的CML细胞中，ERK蛋白被激活素A快速和瞬时激活，表明ERK的磷酸化是CML细胞中激活素A信号传导所必需的。这些结果表明p27 KIP 1的诱导和加塔-1的调节在激活素A诱导的红系细胞分化和凋亡中起重要作用。
p27KIP1 is known as a regulator of cellular differentiation and apoptosis in human cancer cells. We have previously reported that human chronic myeloid leukemia (CML) KU812 and K562 cells show inhibited cellular proliferation in response to treatment with activin A, a member of TGF-beta superfamily. Apoptosis and erythroid differentiation can be induced in KU812 and K562 cells, respectively. We report herein that activin A induced the expression of p27KIP1 in CML cells along with the induction of cellular differentiation and apoptosis. There are putative binding sequences of erythroid-related transcription factor GATA-1 in the promoter region of the human p27KIP1 gene. Expression of GATA-1 protein in activin A-treated KU812 and K562 cells showed dissimilar regulation in these two cell lines. Induction of p27KIP1 was commonly observed, but it did not correspond to the expression levels of GATA-1 in either line of activin A-treated CML cells. In addition, ERK protein was rapidly and transiently activated with activin A in both types of CML cells, suggesting that phosphorylation of ERK is required for activin A signaling in CML cells. These results indicate that both p27KIP1 induction and regulation of GATA-1 play essential roles in activin A-induced erythroid differentiation and apoptosis.