p73 and MDM2 confer the resistance of epidermoid carcinoma to cisplatin by blocking p53 |
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Authors: | Hayashi Syunji Ozaki Toshinori Yoshida Kaori Hosoda Mitsuchika Todo Satoru Akiyama Shin-ichi Nakagawara Akira |
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Affiliation: | Division of Biochemistry, Chiba Cancer Center Research Institute, Chuoh-ku, Japan. |
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Abstract: | 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. |
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Keywords: | Cisplatin KB-3-1 MDM2 p53 p73 |
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