2006 Volume 32 Issue 3 Pages 342-348
Our group has studied about function of a tumor suppressor p53 molecule as a predictive indicator for cancer therapies by using head and neck cancer cells. This molecule plays an important role in carcinogenesis and cancer therapy, because the p53 molecule induces cell-cycle arrest, apoptosis and DNA repair. Mutations of p53 are observed at a high frequency in human tumors, and are recognized in about half of all malignant tumors in humans. An abnormality of the p53 gene might reduce the low efficiency of their cancer therapies. In the both systems of a human cell culture and their transplanted tumor, the sensitivities to radiation and anti-cancer agents were observed in wild-type (wt) p53 cells, but not in mutated (m) or deleted p53 cells. In this review, we discuss the p53 activation signaling pathways after radiation and/or anti-cancer agents. In addition, we applied a chemical chaperone such as glycerol which restores mp53 to wtp53 function through conformational change of mp53. In contrast, we found that high linear energy transfer (LET) particles such as carbon beams introduced efficiently apoptosis in mp53 or deleted p53 cells. Namely, these results suggest that high LET radiations are effective for all patient regardless p53 gene status. From these scientific processes, we confirmed that studies of the p53 molecule are important for cancer science including carcinogenesis from gene stability and cancer therapy from a factor for predicting therapy effectiveness.
