Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73α

Radiation therapy is the most effective therapy for cervical cancer in advanced stages. p53 plays a critical role in the cellular response to radiation-induced DNA damage. However, p53 function is often impaired in the presence of the oncoprotein E6 from human papillomavirus, which is often associated with the development of cervical cancer. p73, a p53 family member, is highly similar to p53, but is resistant to the degradation by human papillomavirus E6. In this study, we investigated the role of p73α in relation to cellular radiosensitivity in the p53-impaired cervical cancer cells. Radiosensitivity and irradiation-induced apoptotic cell death were examined in the exogenous overexpressed p73α- and p53-impaired cells. Our results showed that the endogenous p73α expressed only in the radiosensitive cervical cancer C4-1 cells, but not in the radioresistant SiHa, Caski, and HeLa cells. Overexpression of exogenous p73α by transfection in the radioresistant cells resulted in a significant increase of cellular sensitivity to radiation. Enhanced radiosensitivity in p73α-transfected cells was attributed by increase of cellular apoptosis. Coactivation of p21 was also observed in the p73α-transfected cells upon radiation treatment. In summary, our findings suggested that p73α is an important determinant of cellular radiosensitivity in the p53-impaired cervical cancer cells. [Mol Cancer Ther 2006;5(5):1209–15]