ABSTRACT
PURPOSE: To investigate the effects of Akt/ARK5 pathways on the metastatic potential of human breast cancer cells. MATERIALS AND METHODS: The human ARK5 gene was transfected into MDA-MB-231 cells. Effects of ARK5 on MDA-MB-231 cells were investigated in vitro. The tumorigenicity and spontaneously metastatic capability regulated by ARK5 were determined using an orthotopic xenograft tumor model. RESULTS: ARK5 enhanced the invasive and metastatic potential of MDA-MB-231 cells under regulation by Akt. The enhancement was associated with increasing MMP-2, MMP-9, and MT1-MMP expression. The results were further demonstrated by RNA interference experiment. In an in vivo study, we also demonstrated that ARK5-transfected breast cancer cells grew faster and had more pulmonary metastases than its parental counterparts. CONCLUSION: ARK5 led to a more invasive phenotype and metastatic potential in human breast cancer dependent on Akt.
