p73 and MDM2 confer the resistance of epidermoid carcinoma to cisplatin by blocking p53
- 作者：Syunji Hayashi ; Toshinori Ozaki ; Kaori Yoshida ; Mitsuchika Hosoda ; Satoru Todo ; Shin-ichi Akiyama and Akira Nakagawara
- 关键词：Cisplatin ; KB-3-1 ; MDM2 ; p53 ; p73
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2006
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：18 August 2006
- 卷：347
- 期：1
- 页码：60-66
- 文件大小：344 K
摘要
p73 responds to DNA damage and exerts its pro-apoptotic function. However, p73 might contribute to the development of drug-resistance in certain tumor cells. In this study, we found that p73 and MDM2 correlate with cisplatin-resistant phenotype of human epidermoid carcinoma-derived cells. p73 and MDM2 were kept at low levels in the cisplatin-sensitive KB-3-1 cells, whereas p53 was induced to be phosphorylated at Ser-15 in response to cisplatin. In contrast, p73 and MDM2 were expressed at higher levels, and cisplatin-mediated p53 phosphorylation was undetectable in the cisplatin-resistant KCP-4 cells. Enforced expression of p73 in KB-3-1 cells caused an accumulation of unphosphorylated form of p53 and MDM2, and conferred the cisplatin resistance. Collectively, our results suggest that a loss of the cisplatin sensitivity is at least in part due to a lack of cisplatin-induced p53 phosphorylation, and p73 might cooperate with MDM2 to be involved in this process.