A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines
A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines
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DOI：
10.1006/bbrc.1999.2067
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发表时间：
2000-02-05
影响因子：
3.1
通讯作者：
Namba, M
中科院分区：
文献类型：
--
作者：
Tsuji, T;Miyazaki, M;Namba, M
正常的人类细胞在一定数量的细胞分裂后停止增殖。这种现象被称为细胞老化。衰老表型为显性表型，不朽表型为隐性表型的事实表明，人类细胞的不朽可能是由正常细胞中某些基因的功能丧失引起的。基于这一证据，本实验室利用代表性差异分析（RDA）系统分离了几个在人细胞永生化过程中表达下调的cDNA克隆。其中一种被命名为REIC的基因在3种人永活细胞系中的表达水平低于正常细胞系。此外，REIC在8种人肿瘤源性细胞系（Hep3B和HuH-7肝细胞癌、HuH-6克隆5肝母细胞瘤、HuCCT-1胆管癌、A549肺癌、HaCaT永活角质细胞、HeLa宫颈癌和Saos-2骨肉瘤）中的表达水平也明显降低。相反，在检测的人体组织中，含有大量有丝分裂后细胞的心脏和大脑显示出最高的REIC表达。全长REIC cDNA显示，该蛋白全长350个氨基酸，在每个氨基端和羧基端都具有螺旋状的三级结构。此外，在蛋白质数据库中搜索发现该基因产物与Dkk-3相匹配，Dkk-3是一种新的Wnt癌基因抑制剂。这些结果表明，我们克隆的REIC可能具有肿瘤抑制作用。(C) 2000年学术出版社。
Normal human cells stop proliferation after a certain number of cell divisions. This phenomenon is called cellular aging. The fact that the senescence phenotype is dominant and the immortal one is recessive indicates that immortalization of human cells may be caused by loss of functions of certain genes in normal cells. Based on this evidence, several cDNA clones whose expression was down-regulated during the immortalization process of human cells were isolated by the representative difference analysis (RDA) system in our laboratory. One of them, which was named REIC, was expressed to a lower degree in three human immortalized cell lines as compared with their parental normal counterparts, In addition, the expression of REIC was markedly lower in eight human tumor-derived cell lines (Hep3B and HuH-7 hepatocellular carcinomas, HuH-6 Clone 5 hepatoblastoma, HuCCT-1 cholangiocarcinoma, A549 lung cancer, HaCaT immortalized keratinocyte, HeLa cervical carcinoma, and Saos-2 osteosarcoma). In contrast, among the human tissues examined, the heart and brain, which contain a large number of post-mitotic cells, showed the highest expression of REIC. The full-length REIC cDNA revealed that the predicted protein is 350 amino acids in length and possesses coiled-coil tertiary structures in each of the amino- and carboxyl-termini. Furthermore, a search of the protein database revealed a match of this gene product with Dkk-3, which is a novel inhibitor of Wnt oncogene. These results indicate that the REIC cloned by us may function as a tumor suppressor. (C) 2000 Academic Press.