p73 Expression Is Associated with the Cellular Radiosensitivity in Cervical Cancer after Radiotherapy

• Published in: Clinical cancer research Vol. 10; no. 10; pp. 3309 - 3316
• Main Authors: Liu, Stephanie Si, Leung, Rebecca Ching-Yu, Chan, Kelvin Yuen-Kwong, Chiu, Pui-Man, Cheung, Annie Nga-Yin, Tam, Kar-Fai, Ng, Tong-Yow, Wong, Ling-Chui, Ngan, Hextan Yuen-Sheung
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.05.2004
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Apoptosis; bcl-2-Associated X Protein; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cervix Uteri - metabolism; DNA - chemistry; DNA Methylation; DNA Primers - chemistry; DNA, Complementary - metabolism; DNA, Viral - genetics; Female; Gene Expression Regulation, Neoplastic; Genes, p53; HeLa Cells; Humans; Immunohistochemistry; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prognosis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Radiation Tolerance - genetics; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins - metabolism; RNA - metabolism; Sequence Analysis, DNA; Sulfites - chemistry; Temperature; Time Factors; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - radiotherapy; Radiosensitivity; Treatment; Uterine cervix; Malignant tumor; Gene expression; Radiotherapy; Uterine cervix diseases; Cervical cancer; Female genital diseases
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0119

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy (S. S. Liu et al ., Eur. J. Cancer, 37: 1104–1110, 2001). By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy ( P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients ( P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 ( P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression ( P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.