The roles of REIC gene and its encoding product in gastric carcinoma
The roles of REIC gene and its encoding product in gastric carcinoma
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REIC基因及其编码产物在胃癌中的作用
DOI：
10.4161/cc.19823
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发表时间：
2012-04-01
期刊：
影响因子：
4.3
通讯作者：
Zheng, Hua-chuan
中科院分区：
文献类型：
--
作者：
Xu, Xiao-yan;Xia, Pu;Zheng, Hua-chuan
与亲本正常对应物相比，REIC在永生化细胞系中下调。它可以抑制集落形成、肿瘤生长和诱导细胞凋亡。在此，对用REIC表达质粒、其siRNA转染或用重组REIC处理的胃癌或上皮细胞进行表型测量或相关分子检测。采用RT-PCR、免疫印迹和免疫组化方法检测REIC在胃癌组织中的表达。REIC过表达或处理导致AGS细胞的低核质比和增殖、G（1）停滞、高凋亡、低迁移、侵袭或板状伪足形成。REIC基因敲低在GES-1细胞中引起相反的结果。抗REIC抗体阻断REIC过表达对细胞增殖、G（1）/S进程和凋亡的影响。异位REIC表达下调AGS细胞中β-catenin、磷酸化S6 K（Thr 389）、磷酸化Akt 1/2/3（Ser 473）、cyclin D2和E、WAVE 2的表达，上调磷酸化mTOR（Ser 2448）的表达和Akt 1、Akt 2、mTO R、Raptor和Rictor的mRNA水平。REIC表达与肿瘤大小、淋巴结转移、去分化及预后不良呈负相关。血清REIC水平在健康人中显著高于癌症患者，并且通过ELISA与肿瘤大小呈负相关。REIC的过表达或重组REIC逆转胃癌细胞侵袭性的可能机制是下调β-catenin和WAVE 2的表达，改变其他相关靶蛋白。REIC表达下调与胃癌的侵袭行为和不良预后密切相关。
REIC is downregulated in immortalized cell lines compared with the parental normal counterparts. It may inhibit colony formation, tumor growth and induce apoptosis. Here, gastric carcinoma or epithelial cells transfected with REIC-expressing plasmid, its siRNA or treated with recombinant REIC were subjected to the phenotypes' measurement or related molecules' detection. REIC expression was examined in gastric carcinomas by RT-PCR, western blot and immunohistochemistry. REIC overexpression or treatment resulted in a low karyoplasmic ratio and proliferation, G(1) arrest, high apoptosis, low migration, invasion or lamellipodia formation in AGS cells. REIC knockdown caused the opposite in GES-1 cells. Anti-REIC antibody blocked the effects of REIC overexpression on proliferation, G(1)/S progression and apoptosis. Ectopic REIC expression downregulated the expression of beta-catenin, phosphorylated S6K (Thr389), phosphorylated Akt1/2/3 (Ser473), cyclin D2 and E, WAVE2 and upregulated phosphorylated mTOR (Ser2448) expression and the mRNA level of Akt1, Akt2, mTO R, Raptor and Rictor in AGS cells. REIC expression was negatively associated with tumor size, lymph node metastasis, dedifferentiation or poor prognosis of carcinoma. The serum REIC level was significantly higher in healthy individuals than the carcinoma patients and inversely linked to tumor size by ELISA. The possible mechanisms underlying the forced REIC overexpression or recombinant REIC mediated the reversal of the aggressive phenotypes of gastric carcinoma cells are to downregulate beta-catenin and WAVE2 expression and to alter other related target proteins. Downregulated REIC expression was closely linked to aggressive behaviors and poor prognosis of gastric carcinoma.