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The functional analysis of Erc gene encoding GPI anchor protein

编码GPI锚定蛋白的Erc基因的功能分析

基本信息

批准号：
18500330
负责人：
ZHANG Danqing
金额：
$ 2.63万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500330/
关键词：
Erc Mesothelin gene Tsc2 gene GPI anchor protein knockout mouse Carcinogenesis Erc遺伝子

项目摘要

The Erc (expressed in renal carcinoma) was identified as an inducible gene during the renal carcinogenesis of the Eker (Tsc2 mutant) rat and is a homologue of the human Mesothelin gene. Erc is also overexpressed in the renal carcinoma cell line of the Tsc2 knockout (KO) mouse. To elucidate functional importance of Erc in renal carcinogenesis as well as in mesothelioma, we have performed genetic cross experiments between Tsc2 KO and Erc KO mice. Then we examined influence of the Erc genotype on the development of renal carcinomas in the Tsc2 hetero-mutant mouse. In 32% of male and 20% of female Tsc2 hetero-mutant mice with wild-type Erc, renal carcinomas with a diameter ranging from 4 to 30mm were developed by the age of 18 months. In contrast, all of the renal carcinomas in Tsc2 hetero-mutant mice with Erc homo-mutation had a diameter equal to or less than 2mm. There was no remarkable difference in the size of renal tumors between Tsc2 hetero-/Erc hetero-mutant and Tsc2 hetero-mutant/Erc wild-type mice. These results suggest that Erc may play an important role for tumor proliferation. In addition, we established Tsc2/Erc-deficient renal carcinoma cell lines and then transferred Erc-expression system into them. Adhesion of cell lines to the collagen-coated plate became stronger by overexpression of Erc protein. On the other hand, cell adhesive property was deteriorated when Erc expression was inhibited by RNA interference, suggesting that Erc has a role in the cell-substrate adhesion. Now we are further investigating in vivo function of Erc by implanting the renal carcinoma cell lines into the nude mouse.

Erc（在肾癌中表达）被鉴定为 Eker（Tsc2 突变体）大鼠肾癌发生过程中的诱导基因，并且是人间皮素基因的同源物。 Erc 在 Tsc2 敲除 (KO) 小鼠的肾癌细胞系中也过度表达。为了阐明 Erc 在肾癌发生和间皮瘤中的功能重要性，我们在 Tsc2 KO 和 Erc KO 小鼠之间进行了遗传交叉实验。然后我们检查了 Erc 基因型对 Tsc2 异种突变小鼠肾癌发展的影响。 32% 的雄性 Tsc2 异质突变小鼠和 20% 的雌性野生型 Erc 小鼠在 18 个月大时出现直径为 4 至 30 毫米的肾癌。相比之下，具有Erc同源突变的Tsc2异种突变小鼠中的所有肾癌的直径等于或小于2mm。 Tsc2异种/Erc异种突变体和Tsc2异种突变/Erc野生型小鼠之间肾肿瘤的大小没有显着差异。这些结果表明Erc可能在肿瘤增殖中发挥重要作用。此外，我们还建立了Tsc2/Erc缺陷型肾癌细胞系，然后将Erc表达系统转入其中。通过过度表达 Erc 蛋白，细胞系对胶原包被板的粘附变得更强。另一方面，当RNA干扰抑制Erc表达时，细胞粘附特性恶化，表明Erc在细胞-基质粘附中发挥作用。目前我们正在通过将肾癌细胞株植入裸鼠体内进一步研究Erc的体内功能。