Inhibition of FOXM1 transcription factor suppresses cell proliferation and tumor growth of breast cancer.

The forkhead box M1 (FOXM1) transcription factor regulates the expression of genes essential for cell proliferation and transformation and is implicated in tumorigenesis and tumor progression. FOXM1 has been considered as a potential target for the prevention and/or therapeutic intervention in human carcinomas. In this study, we observed a strong expression of FOXM1 in clinical tissue specimens and cell lines of human breast cancer and a correlation between FOXM1 levels and the proliferation ability in the tested MCF-7, MDA-MB-231 and ZR-75-30 cells. By using an adenovirus vector (named AdFOXM1shRNA) that expresses a short hairpin RNA (shRNA) to downregulate FOXM1 expression specifically, we found that the knockdown of FOXM1 expression diminished the proliferation and anchorage-independent growth of the breast cancer cells. The FOXM1 silencing in ZR-75-30 cells dramatically prevented the tumorigenicity of the AdFOXM1shRNA-treated cells in vitro and in vivo. Furthermore, the efficacy of AdFOXM1shRNA for tumor gene therapy was assessed with the breast cancer xenograft mouse model and the tumor growth was significantly suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumors. Together, our results suggest that FOXM1 is a potential therapeutic target for breast cancer and AdFOXM1shRNA may be an additional gene therapeutic intervention for breast cancer treatment.