Gene expression profiling of oral cancer cells chronic exposed to areca nut extract

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 molecular basis of areca nut associated oral carcinogenesis, we established two oral cell sublines chronically treated with areca nut extract (ANE) at IC70 dose for 2 months. Affymatrix microarray was used in transcriptome profiling between parental and ANE sublines of oral cancer cells. Algorithmic analysis was applied to analyze the network regulatory pathways. RT-PCR was used to validate the genes altered expressions in ANE-sublines. Total of 35 genes was differentially expressed in both sublines. Several functional pathways were apparently altered, with lipid metabolism (P=1.9510), oxidative phosphorylation (P=1.0210), and cell adhesion (P=9.6610) most significant. Seven genes were confirmed over 2-fold of changes, including HMGCS1, KRT-17 up-regulation and SMC4, CENPF, ID-1, IL1-alpha and Ches1 down-regulation. Further study revealed Ches1 was down regulation upon arecoline treatment. Consistently, this gene was reduced expression in 52% of oral cancer tissues, which was significantly correlated with areca nut chewing habit of patients (p = 0.04). Thus, these results provide information regarding the molecular mechanisms of areca nut-induced oral carcinogenesis.