Mol. Cells 2011; 31(6): 579-583
Published online May 11, 2011
https://doi.org/10.1007/s10059-011-0065-z
© The Korean Society for Molecular and Cellular Biology
Hyun-Jung An1,2, Hayyoung Lee3,*, and Sang-Gi Paik1,2,*
Correspondence to : *Correspondence: hlee@cnu.ac.kr (HL); sgpaik@cnu.ac.kr (SGP)
We have previously shown that Ras mediates NO-induced BNIP3 expression via the MEK-ERK-HIF-1 pathway in mouse macrophages, and that NO-induced death results at least in part from the induction of BNIP3. In the present study, we describe another aspect of Ras regulation of BNIP3 expression in pancreatic cancer cells. Human BNIP3 promoter-driven luciferase activity was efficiently induced by activated Ras in AsPC-1, Miapaca-2, PK-1 and PANC-1 cells. However, expression of endoge-nous BNIP3 was not induced, and BNIP3 up-regulation by hypoxia was also inhibited. Treatment of the cells with the DNMT inhibitor, 5-aza-2-deoxycytidine, restored BNIP3 induction, indicating that DNA methylation of the BNIP3 promoter was respon-sible for the inhibition of BNIP3 induction. Furthermore, inhibition of the MEK pathway with U0126 reduced DNMT1 expression, but not that of DNMT3a and 3b, and restored the hypoxia-inducibility of BNIP3, suggesting that the DNA methylation of the BNIP3 promoter was mediated by DNMT1 via the MEK pathway.
Keywords BNIP3, DNMT1, MEK, methylation, Ras
Mol. Cells 2011; 31(6): 579-583
Published online June 30, 2011 https://doi.org/10.1007/s10059-011-0065-z
Copyright © The Korean Society for Molecular and Cellular Biology.
Hyun-Jung An1,2, Hayyoung Lee3,*, and Sang-Gi Paik1,2,*
1Department of Biology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 2Brain Korea 21 Daedeok R&D Innopolis Bio Brain Center, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea, 3Institute of Biotechnology, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea
Correspondence to:*Correspondence: hlee@cnu.ac.kr (HL); sgpaik@cnu.ac.kr (SGP)
We have previously shown that Ras mediates NO-induced BNIP3 expression via the MEK-ERK-HIF-1 pathway in mouse macrophages, and that NO-induced death results at least in part from the induction of BNIP3. In the present study, we describe another aspect of Ras regulation of BNIP3 expression in pancreatic cancer cells. Human BNIP3 promoter-driven luciferase activity was efficiently induced by activated Ras in AsPC-1, Miapaca-2, PK-1 and PANC-1 cells. However, expression of endoge-nous BNIP3 was not induced, and BNIP3 up-regulation by hypoxia was also inhibited. Treatment of the cells with the DNMT inhibitor, 5-aza-2-deoxycytidine, restored BNIP3 induction, indicating that DNA methylation of the BNIP3 promoter was respon-sible for the inhibition of BNIP3 induction. Furthermore, inhibition of the MEK pathway with U0126 reduced DNMT1 expression, but not that of DNMT3a and 3b, and restored the hypoxia-inducibility of BNIP3, suggesting that the DNA methylation of the BNIP3 promoter was mediated by DNMT1 via the MEK pathway.
Keywords: BNIP3, DNMT1, MEK, methylation, Ras
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