Li Xue-Ling, Eishi Yoshinobu, Bai Yun-Qing, Sakai Hidekazu, Akiyama Yoshimitsu, Tani Masao, Takizawa Touichirou, Koike Morio, Yuasa Yasuhito
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8519, Japan.
Int J Oncol. 2004 Feb;24(2):257-63.
SOX2, a SRY-related HMG box protein, is thought to be an important transcription factor during organogenesis, including the stomach although the expression and function are unclear. We investigated SOX2 protein expression to clarify its roles in differentiation and carcinogenesis of the stomach. Using polyclonal SOX2 antibodies, expression of SOX2 in gastric normal mucosae, intestinal metaplasia and carcinomas from 68 gastric carcinoma patients was studied by immuohistochemistry. SOX2 was strongly and moderately expressed in the nuclei of the foveolar epithelium and intestinal metaplasia, respectively, the expression being much higher than that in carcinomas (p<0.0001). Using antibodies to MUC5AC, MUC2 and CD10, the 68 gastric carcinomas were classified into gastric type, intestinal type, mixed gastric and intestinal type, and null type. A significant difference in SOX2 expression was observed between the gastric and intestinal types (p<0.05), with a higher expression in the former than in the latter. Moreover, over-expression of SOX2 induced the mRNA expression of endogenous MUC5AC, a specific mucin marker for the gastric type, in COS-7 cells. Our findings indicate that SOX2 may play a role in differentiation of the human gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type.
SOX2是一种与SRY相关的HMG盒蛋白，被认为是器官发生过程中的一种重要转录因子，包括胃，尽管其表达和功能尚不清楚。我们研究了SOX2蛋白的表达，以阐明其在胃分化和癌变中的作用。使用多克隆SOX2抗体，通过免疫组织化学研究了68例胃癌患者的胃正常黏膜、肠化生和癌组织中SOX2的表达。SOX2分别在胃小凹上皮细胞核和肠化生中呈强表达和中度表达，其表达远高于癌组织（p<0.0001）。使用抗MUC5AC、MUC2和CD10抗体，将68例胃癌分为胃型、肠型、胃肠混合型和无定型。胃型和肠型之间SOX2表达存在显著差异（p<0.05），前者表达高于后者。此外，SOX2的过表达诱导了COS-7细胞中内源性MUC5AC（胃型特异性黏蛋白标志物）的mRNA表达。我们的研究结果表明，SOX2可能在人胃上皮细胞分化中起作用，并且SOX2可能参与胃癌发生，尤其是胃型胃癌。
