Betel quids chewers contribute more than 80% Taiwan's oral cancer patient; therefore, the ingredients of betel quids are under studied and the correlation with cancer had became one of the major topic for researchers in Taiwan. There were several lines of studies for ingredients from betel quids, yet no consistency for the mechanism of betel quids-related oral cancer. We started to approach this issue by examining the signal pathway by betel quids extracts and their major components. We found arecoline, one of the major components of betel quids can induced p42/44 MAP kinase activation and immediate early gene c-jun and c-fos expressions but downstream events and regulation still is an enigma. We would like to continue following this pathway and aim particularly at regulation of c-jun and c-fos. Since degradation of most short-lived regulatory cellular proteins is mediated by the ubiquitin-proteasome pathway, the expression pattern of p42/44 MAP kinases, c-jun and c-fos might also fit into this notion, therefore, we made an hypothesis as following: Arecoline can induce p42/44 MAP kinase phosphorylation, subsequent c-jun and c-fos activation, and the degradation of c-jun and c-fos is ubiquitin-proteasome pathway related. The hypothesis was supported by our experiment using a cDNA clone encoding an ubiquitin-conjugating (UBC) enzyme, showing UBC is expressed in betel quids stimulated NIH 3T3 cells. It was demonstrated that c-jun, c-fos expression were affected by proteosome inhibition.
