Functional cooperation between Stat-1 and ets-1 to optimize icam-1 gene transcription.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the immune system, enabling the interactions between effector cells and target cells. It is also known to be involved in tumor growth and metastasis. Its expression is transcriptionally regulated by several proinflammatory cytokines including IFN-γ, which induces ICAM-1 transcription via the JAK–STAT signaling pathway in a Stat1-dependent fashion. The ICAM-1 promoter contains several cis-active regulatory elements including 2 Ets binding sites (EBSs) located at positions –158 and –138 relatively to the AUG, which were previously shown to play a role in the constitutive activity of the ICAM-1 promoter. In the present study, we have determined whether the EBSs are also involved in the regulation of ICAM-1 gene transcription by pro-inflammatory cytokines. Transient transfection assays were performed with reporter genes containing ICAM-1 promoter constructions cloned upstream from the firefly luciferase gene. Site-specific mutations of the ...