All-trans retinoic acid induces cellular senescence by up-regulating levels of p16 and p21 via promoter hypomethylation

作者：Lim Joo Song; Park Sun Hye; Jang Kyung Lib^*

来源：Biochemical and Biophysical Research Communications, 2011, 412(3): 500-505.

DOI：10.1016/j.bbrc.2011.07.130

• All-trans retinoic acid
• Cellular senescence
• DNA methylation
• Retinoic acid receptor beta(2)
• p21
• p16

All-trans retinoic acid (ATRA) induces cellular senescence via up-regulation of p16 and p21; however, the action mechanism of ATRA is unknown. Here, we show that ATRA induces promoter hypomethylation of p16 and p21 via down-regulation of DNA methyltransferases 1, 3a, and 3b to facilitate binding of Ets1/2 to the p16 promoter and p53 to the p21 promoter, resulting in up-regulation of their expression and subsequent induction of cellular senescence in HepG2 cells. These effects were mediated by retinoic acid receptor 02 whose promoter was also hypomethylated in the presence of ATRA. Therefore, ATRA can be considered as an epi-drug in cancer therapy.

• 出版日期2011-9-2