Inhibition of the Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway Decreases DNA Methylation in Colon Cancer Cells *
作者： Rong Lu , Xia Wang , Zhao-Fei Chen , Dan-Feng Sun , Xiao-Qing Tian
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摘要: Abstract The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) pathway is a critical intermediary for cell proliferation, differentiation, and survival. In the human colon cancer line SW1116, treatment with DNA methyltransferase 1 (DNMT1) inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) or ERK-MAPK inhibitors PD98059 rottlerin, transient transfection MAP/ERK (MEK)1/2 small interfering RNA down-regulates DNMT1 proliferating nuclear antigen levels. this report, we found that drug of SW1116 cells induced promoter demethylation p16INK4A p21WAF1 genes, which up-regulated their mRNA expression Flow cytometry revealed rottlerin cycle arrest at phase G1 (p < 0.05). Thus, siRNA-mediated knockdown decreases methylation via down-regulating other unknown mediator(s) in cells.
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