Abstract
Big mitogen-activated protein kinase 1 (BMK1) is activated by mitogens and oncogenic signals, and is strongly implicated in tumorigenesis. In the present study, it was demonstrated that the activation of BMK1, but not extracellular signal-regulated kinase (ERK)1/2, can induce proliferation in prostate cancer cells. It was found that the proliferation of epidermal growth factor (EGF)-treated cells was accelerated by 40% compared with non-treated cells using a CCK8 assay. In addition, cell cycle analysis using flow cytometry showed that the proportion of cells in the S phase increased significantly in the BMK1-activated PC-3 cells, suggesting that the activation of BMK1 promotes entry into the S phase of the cell cycle in prostate cancer cells. Furthermore, western blot analysis indicated that EGF-mediated activation of BMK1, but not ERK1/2, participates in the proliferation and cell cycle regulation in prostate cancer cells. Furthermore, the effects of cell cycle regulation by the activation of BMK1 were associated with the increased expression levels of cyclin A and cyclin E, whereas the expression of cyclin B and cyclin D1 was unchanged in this process. Therefore, the present study demonstrated that the activation of BMK1 can induce proliferation by promoting entry into the S phase through the upregulation of cyclin A and cyclin E expression levels in prostate cancer cells.