Transfection of nm23-H1 increased expression of -Catenin, E-Cadherin and TIMP-1 and decreased the expression of MMP-2, CD44v6 and VEGF and inhibited the metastatic potential of human non-small cell lung cancer cell line L9981
Abstract:
Nm23 is a metastasis suppressor gene. In this report, we transfected nm23-H1 cDNA into L9981, a human large cell lung cancer cell line with nm23 negative expression, and made a stable transfectant. L9981-nm23-H1 cells exhibited lower cells proliferation rate, more G0/G1 phase growth and an increase in apoptosis with a dramatic decreased in the tumor cells ability to metastasize. L9981-nm23-H1 cells also demonstrated a significantly reduced lymph node and pulmonary metastatic capacity in vivo when injected into the nude mice. Furthermore, we used DNAmicroarray analysis to explore the change in expression of the metastasis-related genes in L9981-nm23-H1 cells. We found that the expression of β-Catenin, E-Cadherin and TIMP-1 were significantly increased while expression MMP-2, CD44v6, and VEGF was dramatically decreased in L9981-nm23-H1, as confirmed by RT-PCR and western blot. These results demonstrated that nm23-H1 can suppress the mobility and metastatic capacity of cancer cells and the molecular mechanism by which nm23-H1 suppresses tumor metastasis may be via increasing the expression of metastasis-related genes such as β-Catenin, E-Cadherin and TIMP-1 and decreasing the expression of MMP-2, CD44V6 and VEGF.