| Summary: | 碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 94 === Recent advances in molecular genetics have revealed that multiple genetic alterations including activation of oncogenes and inactivation of tumor suppressor genes are required for tumor development and progression. K-ras is frequently mutated in colorectal cancer. Previous studies have shown that prostaglandin E2 (PGE2) is involved in intestinal carcinogenesis through its binding to the PGE2 receptor subtypes EP1 and EP4 and activation of downstream pathways. But the molecular mechanisms that link K-ras and PGE2 receptor are currently undefined.
The aim of the present work was to study the association between K-ras and PGE2 receptor .We transfer pcDNA3.1 and pcDNA-K-ras in to HT29 colon cancer cells. The transfected cells and the control cells (empty vector) were analyzed by growth assay and immunoblot. Our data showed overexpression Ras protein led to an increase in cell proliferation with activation of the phosphatidylinosotol-3 Kinase (PI3K)/Akt pathway, an effect likely to be due to inhibits GSK3β(Glycogen synthase kinase 3β)activity. Inhibition of GSK3 stabilizes β-catenin (decrease its degradation) and promotes β-catenin nuclear translocation and transcriptional activation of TCF-regulated gene further induction of COX-2 and activation EP1/EP4. We collected colorectal tumor tissues as well as to confirm tumor tissues were overexpression Ras, PI3K, pAkt and EP1/EP4 protein. In this study, we also confirm in the H29 cells, K-ras does not affect MMP2 secretion. Our result provided colorectal cancer causes K-ras mutation which one newly thinks in the treatment. In addition, EP1/EP4 inhibitor use regarding the colorectal cancer prevention also is the choice which may consider.
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