Department of Gastroenterology, Zhongshan Hospital affiliated with Xiamen University, Fujian Province, China.
J Gastroenterol Hepatol. 2012 Aug;27(8):1395-404. doi: 10.1111/j.1440-1746.2012.07146.x.
Aplasia ras homolog member I (ARHI) is a maternally imprinted tumor suppressor gene. ARHI protein is widely expressed in many types of human tissues; however, its expression is frequently reduced or absent in various tumors and plays a tumor suppressor role for in vitro study. In this study, we investigated the expression level of ARHI in gastric cancer in order to investigate the function of ARHI and signaling pathways that might be linked during gastric cancer development.
ARHI mRNA and protein expression levels were analyzed in primary gastric cancer tissues, adjacent noncancerous gastric tissues and gastric cancer cell lines using semi-quantitative polymerase chain reaction, western blotting and immunohistochemistry, respectively.
Our results showed that both mRNA and protein expression levels of the ARHI gene were significantly downregulated (P < 0.05) in gastric cancer tissues and cell lines compared to the corresponding normal control groups. The protein expression level of ARHI was not associated with age, gender, location of tumor, tumor size or metastasis in patients with gastric cancer. However, a significant correlation between the level of ARHI protein expression and the degree of tumor differentiation and Tumor-Node-Metastasis stage was observed (P < 0.05). Furthermore, results of the methyl thiazolyl tetrazolium and Transwell assays and flow cytometric analysis showed increased cell proliferation, migration and anti-apoptotic capacities in the well-differentiated gastric cancer MKN-28 cell line, which has stably silenced ARHI protein expression.
Our data indicate that ARHI expression is downregulated in human gastric cancer and it may be a novel tumor suppressive target for gastric cancer therapy.
Aplasia ras homolog member I（ARHI）是一种母系印迹的肿瘤抑制基因。ARHI 蛋白在许多类型的人体组织中广泛表达；然而，在各种肿瘤中其表达经常减少或缺失，并在体外研究中发挥肿瘤抑制作用。在本研究中，我们研究了胃癌中 ARHI 的表达水平，以研究 ARHI 的功能及其在胃癌发展过程中可能相关的信号通路。
使用半定量聚合酶链反应、western blot 和免疫组织化学分别分析原发性胃癌组织、相邻非癌性胃组织和胃癌细胞系中 ARHI mRNA 和蛋白的表达水平。
我们的结果表明，与相应的正常对照组相比，胃癌组织和细胞系中 ARHI 基因的 mRNA 和蛋白表达水平均显著下调（P<0.05）。ARHI 蛋白的表达水平与胃癌患者的年龄、性别、肿瘤位置、肿瘤大小或转移无关。然而，ARHI 蛋白表达水平与肿瘤分化程度和肿瘤-淋巴结-转移分期之间存在显著相关性（P<0.05）。此外，噻唑蓝比色法、Transwell 检测和流式细胞术分析的结果表明，在 ARHI 蛋白表达稳定沉默的高分化胃癌 MKN-28 细胞系中，细胞增殖、迁移和抗凋亡能力增强。
我们的数据表明，ARHI 在人胃癌中表达下调，可能是胃癌治疗的一种新的肿瘤抑制靶标。
