胃癌中pi3kakt信号转导通路相关基因变异的生物学意义-biological significance of pi 3 kakt signal transduction pathway related gene variation in gastric cancer.docxVIP

PAGE PAGE 10 胃癌组织 1/50，2%）， 在第 9 内含子存在 A48877G 多态位点（胃癌组织 9/50, 18%）。MFAP3L 与 Glaectin-3 在胃癌组织中表达上调 [IHC 阳性着色率分别为 70.8% (17/24)与 64.0% (16/25)，P=0.027 与 P=0.017 ]。 上述研究表明，PI3K/Akt 信号转导通路中与细胞的增殖、侵袭相关的一组 基因 PIK3CA、AKT2、MFAP3L 以及 Glaectin-3 在胃癌中的表达明显上调。通过 基因突变的筛查，发现 PIK3CA 基因和 AKT2 基因在激酶区存在突变或多态位点， 推测与蛋白激酶的功能改变有关。这组基因在 DNA、mRNA 及蛋白水平发生的 改变可能与胃癌的发生发展有密切关系，与胃癌的生物学行为及临床预后的的关 系有待进一步研究。 [关键词] 磷脂酰肌醇-3-激酶催化亚基α；蛋白激酶B-β；微纤维关联样蛋白-3； IgE结合蛋白；胃癌 Biological Significance of PI3K/AKT Signal Pathway and Related Gene Alteration in Gastric Cancer Abstract PI3K/Akt signal pathway is found to be an important process, which may lie in the center of cell growth regulation. After its activation by growth factors, it exerts regulation on cell cycle, proliferation and apoptosis, as well as the angiogenesis, the telomerase activity and cell invasion, etc. In previous studies, variations of multiple genes in PI3K/Akt pathway had been proved in carcinogenesis, and its relationship to tumor initiation and developlent had been recognized. In our former studies, the expression pattern of gastric cancer (GC) genes was set up by Oligo microarray analysis, in which, the discrepant expression of PI3K and Akt family were found. After the building up of protein expression pattern in colon cancer, a relationship between Galetin-3/MFAP3L(a novel protein gene) and PI3K/Akt was proved with high expression. In order to explore the expression changes of PI3K/Akt pathway related genes, PIK3CA, AKT2, Galetin-3 and their mutual relationship, RT-PCR, Western-blot and microarray IHC were used to testify their manifestation in gastric cancer cell lines and primary stomach tumors. The results showed that: PIK3CA and its protein were highly expressed in gastric cancer cell lines and primary tumor (higher mRNA expression in primary tumors 70% 19/29, P=0.01); the MFAP3L, Galetin-3 protein were highly expressed in gastric cancer micro tissue array (IHC positively staining rates: 70.8%, 17/24, P=0.027; 64.0%, 16/25, P=