| Summary: | 碩士 === 長庚大學 === 醫學生物技術研究所 === 97 === Oral cancer is the 6th most frequent cancer in Taiwan. The habit of areca nut chewing is the main etiological factor of oral cancer. To shed light on the phenotype characterization and molecular basis of areca nut associated oral carcinogenesis, we established three oral cancer sublines chronically treated with areca nut extract (ANE) at IC70 dose for 2 months. Cell growth of the ANE subline was decreased, with 0.8 to 0.3 fold of reduction compared to the parental cells. Nevertheless, cell invasion ability was significantly increased in all three sublines, with approximately 5 to 16 folds of elevation. Although various levels in different cell lines, these ANE-sublines exhibited more resistance to stress (cisplatin and radiation) in general, that was associated with higher ROS clearance ability in the subline cells. cDNA microarrays were used in transcriptome profiling between parental and ANE sublines of oral cancer cells. Heretical cluster and algorithmic analyses of the microarray data revealed several pathways significantly associated with ANE (p< 10E-5), as homeostasis, immune response, cell adhesion and signaling pathway response to stimulus. Specially, CHES1 mRNA expressions were decreased in ANE sublines by RT-PCR assay. In addition, CHES1 overexpression arrested cell cycle at G2/M phase might through activating Erk pathway. Clinical study further showed that CHES1 was under expressed in oral cancer tissues. Therefore, the phenotype characterization and transcriptome profiling of oral mucosa cells chronically exposed to areca nut extract were determined. This study may contribute to clinical investigation as risk assessment.
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