Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73alpha.
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 p73alpha 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 p73alpha- and p53-impaired cells. Our results showed that the endogenous p73alpha expressed only in the radiosensitive cervical cancer C4-1 cells, but not in the radioresistant SiHa, Caski, and HeLa cells. Overexpression of exogenous p73alpha by transfection in the radioresistant cells resulted in a significant increase of cellular sensitivity to radiation. Enhanced radiosensitivity in p73alpha-transfected cells was attributed by increase of cellular apoptosis. Coactivation of p21 was also observed in the p73alpha-transfected cells upon radiation treatment. In summary, our findings suggested that p73alpha is an important determinant of cellular radiosensitivity in the p53-impaired cervical cancer cells.
Liu
Stephanie Si
SS
Department of Obstetrics and Gynaecology, Queen Mary Hospital, 6th Floor, Professorial Block, Pokfulam Road, Hong Kong SAR, China.
Chan
Kelvin Yuen-Kwong
KY
Leung
Rebecca Ching-Yu
RC
Law
Helen Ka-Wai
HK
Leung
Tsin-Wah
TW
Ngan
Hextan Yuen-Sheung
HY
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins