Research On The Mechanism Of E2F1 Regulating ICAM-1 In Cancer Cells

Intercellular adhesion molecule-1 (ICAM-1) encodes a cell surface glycoprotein which is typically expressed on endothelial and immune cells. ICAM-1 binds to two integrins belonging to the CD18 family, i.e., LFA-1 (CDlla/CD18) and Mac-l (CDllb/CD18) in lymphcytes and macrophage, respectively. ICAM-1 plays an important role in inflammatory processes and in the T-cell mediated host defense. It is also reported that ICAM-1 plays a critical role in tumor metastasis.Cytokines released during pathologic conditions, such as IFN-γ, IL-1 and TNF-αcan upregulate ICAM-1's expression. Some clinical studies showed that ICAM-1 has higher expression in many cancer cells. It is reported that NF-κB can regulate transcription of ICAM-1 in endothelial cells. However, the mechanism of regulation of ICAM-1 is indetermined yet.Our previous study found that there is a relationship between expression of E2F1 and ICAM-1 in a prostate cancer cell line DU145. In this study we showed that the expression of ICAM-1 was increased at both mRNA and protein level when E2F1 was knocked down in PC3 and Hela cells. Conversely, overexpression of E2F1 attenuated ICAM-1 expreesion, indicating that E2F1 may downregulate expression of ICAM-1.Further, dual luciferase reporter assays with ICAM-1 promoter verified that E2F1 downregulated transcription expression of ICAM-1 through NF-κB binding sites within promoter region of ICAM-1.The study further verified our earlier findings that E2F1 able to down-regulate ICAM-1 in variety cell types. Considering the role of ICAM-1 in tumor metastasis, suggesting that E2F1 may be a target for inhibition of tumor metastasis.