골육종 세포주에서 ERK1/2 활성화에 의한 matrix metalloproteinase 2 활성화와 ezrin 발현 조절

Abstract

Purpose: In this study, we aimed to investigate the influence of mitogen-activated protein kinase (MAPK) signal pathway and related factors of metastatic property on the osteosarcoma cell lines.

Materials and Methods: Osteosarcoma cell lines, MG-63, HOS, U2OS, SAOS-2, and osteoblast-like cell line, MC3T3-E1 were used for evaluating the activation of MAPK signal pathway and the effect of ERK1/2 inhibiton by 15 μM U0126 for 6 days. Then we measured the activity of matrix metalloproteinases (MMP) by gelatin zymography analysis.

Results: ERK was strongly activated in three osteosarcoma cell lines, MG-63, HOS, U2OS, and was weakly activated in SAOS-2 cell line. MMP2 was strongly activated in MG-63, HOS, U2OS cell lines. However, SAOS-2 cell line, in which ERK1/2 was weakly activated, showed weak activation of MMP2. When the ERK1/2 was inhibited by U0126 for 6 days, the ezrin expression was remarkably suppressed in all osteosarcoma cell lines. These data showed that the suppression of ezrin expression might be dependent on the ERK1/2 activation in osteosarcoma cell lines.

Conclusion: Our results suggested that the ERK1/2 activation might be related to the activity of MMP2 and the suppression of ezrin expression in osteosarcoma cell lines. We suggest that ERK1/2 activation might be closely related to the ezrin expression and the ezrin expression might play an important role in the activation of MMP2 which is known to involve in the activated MMP2 involves in early metastatic properties in osteosarcoma.