Reciprocal expressions of cyclin E and cyclin D1 in hepatocellular carcinoma

Reciprocal expressions of cyclin E and cyclin D1 in hepatocellular carcinoma
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DOI:
10.1016/s0304-3835(01)00403-7
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发表时间:
2001-07-10
期刊:
影响因子:
9.7
通讯作者:
Kim, CM
Kim, CM
中科院分区:
医学1区
文献类型:
--
作者:
Jung, YJ;Lee, KH;Kim, CM

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G1期细胞周期蛋白、细胞周期蛋白E和细胞周期蛋白D1基因的过度表达导致的细胞周期失调已被证明是人类癌症发展的先决条件。最近,细胞周期蛋白E被认为是足够的G1细胞周期的进展,没有细胞周期蛋白D1。在这里,我们表明,所提出的模型系统是专门存在于人类肝细胞癌(HCC)不同于其他人类癌症。在31例肝癌组织中,21例(67.7%)细胞周期素E蛋白过表达。与cyclin E基因表达相反,cyclin D1在19例(61.2%)HCC中表达显著下调。有趣的是,65%的HCC组织中细胞周期蛋白E基因过表达的细胞周期蛋白D1表达下调,表明这些细胞周期蛋白在细胞周期的G1期进展中相互失调。Southern杂交结果显示,细胞周期素E基因在肝癌组织中有扩增,并呈高水平过表达。目前的研究结果表明,细胞周期蛋白E缺乏细胞周期蛋白D1表达的相互失调可能在G1进展和肝癌的发展中发挥作用。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Deregulation of the cell cycle by overexpression of G1 cyclins, cyclin E and cyclin D1 genes, has been demonstrated to be a prerequisite for the development of human cancer. Recently, cyclin E is proposed to be sufficient for the progression of the G1 cell cycle without cyclin D1. Here we show that the proposed model system was specifically present in human hepatocellular carcinoma (HCC) unlike other human cancers. Of 31 HCC tissues analyzed, 21 (67.7%) exhibited an overexpression of cyclin E protein. In contrast to cyclin E gene expression, cyclin D1 expression was strongly downregulated in 19 (61.2%) HCCs. Interestingly, 65% of HCC tissues with overexpression of the cyclin E gene exhibited downregulation of cyclin D1, suggesting reciprocal deregulation of these cyclins in the G1 progression of the cell cycle. Southern blot analysis proved the amplification of cyclin E gene in HCC with a high level of overexpression. The present findings suggest that the reciprocal deregulation of cyclin E lacking cyclin D1 expression might play a role in G1 progression and the development of HCC. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.