The functional analysis of Erc gene encoding GPI anchor protein

Erc（在肾癌中表达）被鉴定为Eker（Tsc 2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Tsc 2敲除（KO）小鼠的肾癌细胞系中也过表达。为了阐明Erc在肾癌发生以及间皮瘤中的功能重要性，我们在Tsc 2 KO和Erc KO小鼠之间进行了遗传交叉实验。然后，我们研究了Erc基因型对Tsc 2异源突变小鼠肾癌发展的影响。在32%的雄性和20%的雌性Tsc 2野生型Erc异源突变小鼠中，在18个月龄时发生直径范围为4至30 mm的肾癌。相反，在具有Erc同源突变的Tsc 2异源突变小鼠中，所有肾癌的直径等于或小于2 mm。Tsc 2 hetero-mutant/Erc hetero-mutant和Tsc 2 hetero-mutant/Erc野生型小鼠之间的肾肿瘤大小没有显著差异。这些结果表明，Erc可能在肿瘤增殖中起重要作用。此外，我们建立了Tsc 2/Erc缺陷的肾癌细胞系，并将Erc表达系统导入其中。Erc蛋白的过度表达使细胞系与胶原包被的板的粘附变得更强。另一方面，当Erc表达被RNA干扰抑制时，细胞粘附性恶化，表明Erc在细胞-底物粘附中起作用。目前，我们正在通过将肾癌细胞株移植到裸鼠体内，进一步研究Erc的体内功能。

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.