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K-562

维基百科,自由的百科全书

K-562人类永生化骨髓性白血病细胞系,处于高度未分化状态,并且属于红白血病(erythroleukemia)细胞系,具有恶性程度高、增殖速度快,以及可被一系列体外诱导剂诱导分化的特点[1]。最初分离自一名处于急性期的53岁女性慢性骨髓性白血病(CML)患者的胸水[2][3]

特征

K-562细胞不粘连且圆形,对bcr:abl融合基因呈阳性反应,并且与未进行细胞分化粒细胞[4]红细胞[5]蛋白质组相似。在细胞培养的过程中,它们的结块比许多其他悬浮细胞系要少得多,原因可能是由于细胞表面粘附分子引起的bcr:abl融合基因下调[6]。然而有研究表明,过度表达bcr:abl融合基因可能会增加细胞对细胞培养皿的粘附力[7]

K-562细胞可以自发形成类似于早期红细胞粒细胞单核细胞的特征[8],并且由于缺乏抑制自然杀伤细胞活性所需的主要组织相容性复合体[3],因此很容易被自然杀伤细胞杀死[9] 。它们也没有任何痕量的爱泼斯坦-巴尔病毒和其他疱疹病毒。除了费城染色体外,它们在15号染色体的长臂与17号染色体之间表现出第二种的相互易位[2]。 K-562细胞有两个子系可以表示MHC1类分子A2[10]和A3[11]

细胞周期与调控

在生长、细胞分化和凋亡方面,许多因素和成分在K-562细胞的细胞周期中发挥作用[12]。这些白血病细胞的生长受到细胞分化或凋亡的控制[13]。这些未分化的祖细胞中的脱乙酰基酶活性可以诱导细胞分化,从而改变K-562细胞的表型和形态[12]。这些变化还可以使白血病细胞进入应激状态,从而提高细胞对引发凋亡的药物的敏感性[12]。此外,表型的变化会降低生长速率,并且导致K562细胞具有能够向红细胞系、粒细胞系、单核细胞-巨噬细胞系统和巨核细胞系统分化的潜能,表现出相应的细胞表型[14][15],能够在低氧环境下被诱导分化形成红细胞和巨核细胞,故而是用于研究红系诱导分化的理想细胞模型,目前已经成为研究细胞分化的主要细胞模型[16][17]

K-562细胞及许多癌细胞均存在着Aurora激酶英语Aurora kinase过多的问题[18]。Aurora激酶在纺锤体形成、染色体分离及胞质分裂中都发挥作用[18] ,而这些功能在细胞中是必需的,以便分裂和再生组织,并且起维持稳态的作用。然而过度表达Aurora激酶会导致细胞分裂时不受控制,从而导致癌症[18] 。因此,抑制Aurora激酶是癌症的重要调控机制,因为它可以防止细胞进行有丝分裂[18]

细胞凋亡是调节K-562细胞的重要机制,并且可通过细胞代谢状态的变化来诱导[12]。细胞凋亡过程中涉及许多不同的细胞成分,例如BCR/ABL、Bcl-2英语Bcl-2Bax英语Bcl-2-associated X protein蛋白和细胞色素c[13],而p53蛋白在K-562细胞的细胞周期调控中也十分重要[19],因为它靶向细胞周期蛋白依赖性激酶抑制剂p21,引起细胞分化、细胞周期停滞在G1期,最终导致细胞凋亡[19]。当这些成分的水平降低时,它们将不能抑制癌细胞的凋亡,或者会导致细胞凋亡被诱导[13] 。这些成分是线粒体中的关键因素,因此有证据支持细胞凋亡会使用到线粒体凋亡途径[13]。除此之外,当这些细胞成分偏离平衡点时,就会令细胞的形态出现变化,导致K-562细胞停滞在G2/M期[13],从而导致核碎裂、染色质浓缩和其他形态学变化,最终导致细胞程序性死亡[13]

目前已知伊马替尼可以抑制BCR/ ABL,导致细胞停止生长并开始凋亡[20]。K-562细胞的另一个重要调节器是Sirtuin英语Sirtuin[12],通过与细胞中的脱乙酰酶活性相互作用而在细胞应激、代谢和自噬中发挥作用[12]。其他调节K-562细胞的方法包括重楼皂苷 D(polyphyllin D),它会令细胞从祖细胞状态中进行分化并开始凋亡[13]

参考资料

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