2013年5月
The Arf/p53 Protein Module, Which Induces Apoptosis, Down-regulates Histone H2AX to Allow Normal Cells to Survive in the Presence of Anti-cancer Drugs
JOURNAL OF BIOLOGICAL CHEMISTRY
- 巻
- 288
- 号
- 19
- 開始ページ
- 13269
- 終了ページ
- 13277
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M112.402560
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Anti-cancer drugs generally target cancer cells rather than normal somatic cells. However, the factors that determine this differential sensitivity are poorly understood. Here we show that Arf/p53-dependent down-regulation of H2AX induced the selective survival of normal cells after drug treatment, resulting in the preferential targeting of cancer cells. Treatment with camptothecin, a topoisomerase I inhibitor, caused normal cells to down-regulate H2AX and become quiescent, a process mediated by both Arf and p53. In contrast, transformed cells that harbor mutations in either Arf or p53 do not down-regulate H2AX and are more sensitive to drugs unless they have developed drug resistance. Such transformation-associated changes in H2AX expression rendered cancer cells more susceptible to drug-induced damage (by two orders of magnitude). Thus, the expression of H2AX and gamma H2AX (phosphorylated form of H2AX at Ser-139) is a critical factor that determines drug sensitivity and should be considered when administering chemotherapy.
- リンク情報
- ID情報
-
- DOI : 10.1074/jbc.M112.402560
- ISSN : 0021-9258
- PubMed ID : 23536184
- Web of Science ID : WOS:000318850300013