Figure 6

A schematic model whereby E2F1 regulates the ICAM-1 mediated anti-tumor immune circuit through NF-κB modulation. NF-κB binding site is required for E2F1 regulation of ICAM-1. E2F1 interacts with NF-κB forming an NF-κB/E2F1 complex. E2F1 acts as a suppressor to prevent the NF-κB p65/p50 complex from binding to ICAM-1 promoter. As a consequence, E2F1 interferes with the adhesion of monocytes onto prostate cancer cells, the sensitivity of tumor cells to the cytotoxic effect of cytokine-induced killer cells and the growth of prostate cancer cells. Targeted knockdown of E2F1 does not affect the expression of phosphorylation of NF-κB p65 and IκBα, but releases NF-κB p65 to facilitate p65/p50 heterodimerization and binding to the ICAM-1 promoter. Subsequently, ICAM-1 transcription and production are induced, resulting in the enhanced immune cells mediated cytotoxicity against prostate carcinoma cells.