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Research Articles: Therapeutics

Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73

Departments of ¹ Obstetrics and Gynaecology, ² Pathology, and ³ Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China

Requests for reprints: Hextan Yuen-Sheung Ngan, Department of Obstetrics and Gynaecology, Queen Mary Hospital, 6th Floor, Professorial Block, Pokfulam Road, Hong Kong SAR, China. Phone: 852-28554684; Fax: 852-28550947. E-mail: hysngan{at}hkucc.hku.hk

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 p73 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 p73- and p53-impaired cells. Our results showed that the endogenous p73 expressed only in the radiosensitive cervical cancer C4-1 cells, but not in the radioresistant SiHa, Caski, and HeLa cells. Overexpression of exogenous p73 by transfection in the radioresistant cells resulted in a significant increase of cellular sensitivity to radiation. Enhanced radiosensitivity in p73-transfected cells was attributed by increase of cellular apoptosis. Coactivation of p21 was also observed in the p73-transfected cells upon radiation treatment. In summary, our findings suggested that p73 is an important determinant of cellular radiosensitivity in the p53-impaired cervical cancer cells. [Mol Cancer Ther 2006;5(5):1209–15]

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Received 11/ 1/05; revised 2/21/06; accepted 3/15/06.

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