KIF20A mRNA and Its Product MKlp2 Are Increased During Hepatocyte Proliferation and Hepatocarcinogenesis
KIF20A mRNA and Its Product MKlp2 Are Increased During Hepatocyte Proliferation and Hepatocarcinogenesis
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DOI：
10.1016/j.ajpath.2011.09.040
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发表时间：
2012-01-01
影响因子：
6
通讯作者：
Sobczak-Thepot, Joelle
中科院分区：
文献类型：
--
作者：
Gasnereau, Isabelle;Boissan, Mathieu;Sobczak-Thepot, Joelle
有丝分裂驱动蛋白样蛋白2（MKlp 2）是一种微管相关的马达，在有丝分裂退出过程中是细胞因子的最后一步所必需的。它也有助于囊泡从高尔基体到内质网的逆行运输。编码MKlp 2的KIF 20 A基因由E2 F-视网膜母细胞瘤蛋白-p16通路控制，并且在胎儿和增殖的成人组织中发现其广泛表达的mRNA。然而，尚未研究MKlp 2在成人肝脏中的表达模式和功能。我们在此报告MKlp 2在部分肝切除术后小鼠肝再生过程中在体内瞬时积累，并且在肿瘤前和肿瘤小鼠肝脏中强烈过表达。在体外，在有丝分裂原刺激的原代肝细胞中，MKlp 2在细胞周期的G2期期间在细胞核中积累，与有丝分裂激酶Aurora B一致。人肝癌细胞系表现出高水平的MKlp 2;然而，在正常人肝细胞中检测不到。RNAi介导的肝癌细胞中MKlp 2敲低诱导多倍体化，这与其促进胞质分裂的基本功能一致，并抑制细胞增殖而不诱导凋亡。KIF 20 A mRNA在大量的人肝细胞癌中大量积累，在基因组不稳定的肿瘤中观察到最高表达。MKlp 2在正常增殖、癌前和转化肝细胞中的积累表明MKlp 2有助于正常和病理性肝细胞增殖，并且与人肝细胞癌中的肿瘤侵袭性相关。(Am J Pathol 2012，180：131-140; DOI：10.1016/j.ajpath.2011.09.040）
Mitotic kinesin-like protein 2 (MKlp2), a microtubule-associated motor, is required during mitosis exit for the final step of cytokine;is. It also contributes to retrograde vesicular trafficking from the Golgi apparatus to the endoplasmic reticulum in interphase. The KIF20A gene encoding MKlp2 is controlled by the E2F-retinoblastoma protein-p16 pathway, and its widely expressed mRNA is found in fetal and proliferating adult tissues. The expression pattern and function of MKlp2 in the adult liver, however, have not been investigated. We report herein that MKlp2 transiently accumulates in vivo during mouse liver regeneration after partial hepatectomy and is strongly overexpressed in preneoplastic and neoplastic mouse liver. In vitro in mitogen-stimulated primary hepatocytes, MKlp2 accumulated in the nucleus during the G2 phase of the cell cycle coincident with the mitotic kinase Aurora B. Human hepatoma cell lines exhibited high levels of MKlp2; however, it was undetectable in normal human hepatocytes. RNAi-mediated MKlp2 knockdown in hepatoma cells induced polyploidization consistent with its essential function in promoting cytokinesis and inhibited cell proliferation without inducing apoptosis. KIF20A mRNA was strongly accumulated in a large series of human hepatocellular carcinomas, with the highest expression observed in tumors with genomic instability. Accumulation of MKlp2 in normal proliferating, preneoplastic, and transformed hepatocytes suggests that MKlp2 contributes to both normal and pathologic hepatocyte proliferation and is linked to tumor aggressiveness in human hepatocellular carcinomas. (Am J Pathol 2012, 180:131-140; DOI: 10.1016/j.ajpath.2011.09.040)