FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors.

摘要: Forkhead box M1 (FoxM1) transcription factor is known to play important role in human cancers which, part, mediated by its ability modulate cell cycle regulatory proteins as well genes involved proliferation and differentiation. In breast cancer, FoxM1 down-regulation increasingly being recognized an mechanism for the targeted activity of anti-cancer agents. However, mechanistic insight support aggressive cancer poorly understood. We have tested biological consequence up-regulation lines found that MDA-MB-231 SUM149 cells siRNA approach inhibited growth, clonogenicity, migration, invasion. also decreased expression CDK2 E2F1 with concomitant increase p21 p27 proteins, suggesting progression. contrast, over-expression cDNA transfection, (SUM102 SKBR3) expressing low levels FoxM1, resulted increased proliferation, Moreover, many factors are degradation extra cellular matrix angiogenesis such uPA, uPAR, MMP-2, MMP-9, vascular endothelial growth (VEGF) MMP-9 VEGF. Interestingly, uPA transfection abrogated effects were observed FoxM1. Taken together, these results suggest potential application a novel treatment cancer.