C-Myc Overexpression Promotes Osteosarcoma Cell Invasion via Activation of MEK-ERK Pathway

Oncol Res. 2012;20(4):149-56. doi: 10.3727/096504012x13522227232237.

Abstract

Osteosarcoma is a highly metastatic malignancy often with poor prognosis. c-Myc amplification is implicated in osteosarcoma pathogenesis. However, the role of c-myc overexpression in osteosarcoma cell invasion remains unexplored. This study showed that c-myc overexpression enhanced MG-63 and SAOS-2 osteosarcoma cell invasion. Treatment of MEK inhibitor PD98059 or PI3K inhibitor LY294002 decreased cell invasion along with downregulation of MMP-2 and MMP-9 expression. c-Myc overexpression stimulated MEK-ERK pathway whereas inhibited the activity of PI3K-AKT pathway. Specifically, inhibition of MEK-ERK pathway by PD98509 blocked the enhancement effect on cell invasion as well as MMP-2 and MMP-9 expression. The present study demonstrates that c-myc overexpression promotes osteosarcoma cell invasion, probably via activation of MEK-ERK pathway.

MeSH terms

  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Neoplasm Invasiveness
  • Osteosarcoma / pathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Proto-Oncogene Proteins c-myc / physiology*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9