| Summary: | 碩士 === 國立成功大學 === 口腔醫學研究所 === 100 === In clinical, tumor markers can be use to help cancer diagnosis , predict the patient’s response to particular therapies and follow-up disease. The squamous cell carcinoma antigen (SCCA) is a tumor marker and has a clinical value. In clinical diagnosis, patients with higher expression of SCCA show poor prognosis. However, SCCA in clinical use was more than 20 years, but the biological function and mechanism still remain unclear. Our previous studies, we found that overexpression of SCCA led to drug resistance, such as RSV (Resveratrol) and Cisplatin. Cancer cells usually grow faster than normal cells. In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed the “Warburg effect”. Many cancer cells consume glucose and produce lactic acid and cause acidification of the tumor extracellular environment. Acidification of the tumor extracellular environment may promote tumor formation and metastasis. In our previous studies showed the SCCA is a lysosomal proteases inhibitor and could inactivate cathepsin L and anti-cell death. This study we show the cancer cells cultured in low pH (Acidosis) media, increase SCCA expression. The cancer cells culture in low pH (Acidosis) media display drug resistance of RSV (Resveratrol) and Cisplatin. The acidosis enhances the formation of reactive oxygen species (ROS) and induces MAPK signaling pathway and transcription factor, CREB phosphorylation. The cancer cells treated with ROS scavenger reduce SCCA expression and CREB phosphorylation in acidosis condition. We found that, there is a CREB binding region in the promoter region of SCCA1 gene. These results suggested that acidosis increased phosphorylation of the transcription factor CREB via ROS, and them increased its transcriptional activity. Taken together, we suggest cancer resist drug-induced cell death in acidosis condition is through ROS-increased CREB transcriptional activity to promote SCCA1 gene expression .
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