P-0031 Pathobiological Significance of Arhi Expression in Human Gastric Carcinoma and The Precancerous Lesions as Well as Gastric Cancer Cell Lines

Abstract

IntroductionAplesia Ras homologue member I (ARHI, DIRAS3) is a maternally imprinted tumor suppressor gene which is frequently lost in breast and ovarian cancers, and results in autophagic cell death of human ovarian cancer cells in vitro. There has been no report in PMC about ARHI in human gastric carcinomas and gastric cancer cell lines so far. MethodsThe ARHI expression in 309 cases of gastric carcinomas (GCs), with corresponding normal gastric mucosa and the precancerous lesions was investigated immunohistochemically, and the prognostic value of ARHI expression was analyzed. ARHI mRNA and protein expressions in gastric cancer cell lines BGC823, MGC803, SGC7901, MKN45, NCI-N87 and normal gastric epithelial cell line GES-1 were also evaluated using quantitative real time PCR(qrtPCR) and immunofluorescence (IF) methods. ResultsThe positive expression of ARHI protein in intestinal metaplasia (76.1%, 86/113), dysplasia (50.0%, 8/16) and gastric carcinoma (29.8%, 92/309) were down-regulated compared with corresponding normal gastric mucosa (87.4%, 270/309), P<0.05. The rates of ARHI up-regulated and down-regulated expression were 9.7% (30) and 67% (207), the median patients survival time of up-regulated group (62.3 months) was longer than that of down-regulated group (36.7 months). The results of qrtPCR showed that mRNA level of ARHI in the gastric carcinoma cell lines BGC-823, MGC-803 SGC-7901, MKN-45, and NCI-N87 are 0.41, 0.41, 1.39, 1.53, 0.88 fold of gastric cell line GES, respectively. ARHI protein expression detected by IF and Western blot in the cell lines mentioned above accord with the ARHI mRNA expression by qrtPCR in the study. ConclusionWe report, for the first time, that tumor suppressor ARHI expression is mainly down regulated in human gastric carcinoma and gastric dysplasia, suggesting ARHI gene plays important roles in gastric carcinogenesis, in which ARHI related autophagy may be involved. Further study is needed in this field.