Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
Heat shock protein90 (Hsp90) is a molecular chaperone that plays an important role in the stability of unstable proteins. Hsp90 is involved with maintaining the conformation and function of key client proteins involved in cell proliferation and cell cycle progression. Tumor Hsp90 is present entirely in multi-chaperone complexes. Thus, it can become an effective means in cancer therapeutics to disrupt chaperone functions of Hsp90.17-Allylamino-17-demethoxygeldanamycin (17-AAG) which inhibits Hsp90 has effect on apoptotic processes such as the phosphatidyleinositide 3-kinase-Akt kinase cascade. The combination of radiation and 17-AAG extremely increases cell killing. There is a possibility that the enhancement of radiation induced cell killing by 17AAG would not only relate to apoptosis but DSB repair inhibition. So we investigated whether 17-AAG affects DSB repair using two human carcinoma cell lines. These cell lines were then incubated in medium containing 17-AAG 24hr before X-ray exposure in all experiments. Constant field gel electrophoresis clearly indicated that rejoining of DSBs was impaired when exposed to both X-ray and 17-AAG. Furthermore, we are investigating which DSB repair process namely, NHEJ or HR, is principally affected.
