title: p38 MAPK regulates the expression of ether à go-go potassium channel in human osteosarcoma cells.
abstract: BACKGROUND
  The ether à go-go (Eag) channel has been shown to be overexpressed in a variety of cancers. However, the expression and function of Eag in osteosarcoma are poorly understood. In addition, the molecular mechanisms responsible for Eag overexpression in cancer cells remain unclear.
  
  
  METHODS
  The expression of Eag in human osteosarcoma cell line MG-63 was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The effect of Eag inhibition on MG-63 cell proliferation was assessed in vitro. The effect of short hairpin RNA (shRNA) mediated knockdown of Eag on osteosarcoma growth was evaluated in xenograft model in vivo. The activation of mitogen-activated protein kinase (MAPK) pathway and p53 in MG-63 cells was detected by Western blot analysis.
  
  
  RESULTS
  Eag was overexpressed in MG-63 cells. Imipramine or Eag shRNA significantly suppressed the proliferation of MG-63 cells in vitro and in vivo. MG-63 cell proliferation was specifically inhibited by p38 MAPK inhibitor SB203580 or small interference RNA (siRNA). The inhibition of p38 MAPK activation by SB203580 or siRNA reduced Eag protein level but increased p53 protein level. Moreover, the activation of p53 by nutlin-3 induced cell growth arrest in MG-63 cells and reduced Eag protein level, while the inactivation of p53 by pifithrin-alpha (PFT-α) promoted MG-63 cell growth and increased Eag protein expression.
  
  
  CONCLUSIONS
  Eag channel functions as an oncogene to promote the proliferation of human osteosarocma cells. Furthermore, the high expression of Eag in osteosarcoma cells is regulated by p38 MAPK/p53 pathway.
authors: Department of Neurology, the Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China.
authors: Xinyu
authors: X
authors: Wu
authors: Daixing
authors: D
authors: Zhong
authors: Bin
authors: B
authors: Lin
authors: Wenliang
authors: W
authors: Zhai
authors: Zhenqi
authors: Z
authors: Ding
authors: Jin
authors: J
authors: Wu
keywords: Ether à go-go; MAPK pathway; cell proliferation; osteosarcoma; p53