ERK5 is a Target for Gene Amplification at 17p11 and Promotes Cell Growth in Hepatocellular Carcinoma by Regulating Mitotic Entry
ERK5 is a Target for Gene Amplification at 17p11 and Promotes Cell Growth in Hepatocellular Carcinoma by Regulating Mitotic Entry
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DOI：
10.1002/gcc.20624
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Yoshikawa, Toshikazu
中科院分区：
文献类型：
--
作者：
Zen, Keika;Yasui, Kohichiroh;Yoshikawa, Toshikazu
利用高密度寡核苷酸芯片，我们研究了肝细胞癌细胞系的DNA拷贝数异常，并在17p11处检测到一种新的扩增。为了确定17p11的扩增目标，我们定义了扩增片段的范围，并检测了肝癌细胞系在750kb共同扩增区域中所有七个基因的表达。编码细胞外调节蛋白激酶(ERK)5的丝裂原活化蛋白激酶(MAPK)7在扩增该基因的细胞系中过表达。66例原发性肝细胞癌中有35例MAPK7基因拷贝数增加。小干扰RNA下调MAPK7的表达抑制了SNU449细胞的生长，SNU449细胞是MAPK7扩增和过表达最大的肝癌细胞系。ERK5在细胞周期的G2/M期被磷酸化，调节SNU449细胞进入有丝分裂。综上所述，我们的结果提示MAPK7可能是17p11扩增的靶点，NIAPK7的ERK5蛋白产物可能通过调节有丝分裂进入促进肝癌细胞的生长。(C)2008年Wiley-Liss，Inc.
Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase(ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of NIAPK7 promotes the growth of HCC cells by regulating mitotic entry. (c) 2008 Wiley-Liss, Inc.