TRANSCRIPTIONAL MODULATION OF THE HUMAN INTERCELLULAR-ADHESION MOLECULE GENE-I (ICAM-1) BY RETINOIC ACID IN MELANOMA-CELLS

Retinoids play an important role as differentiating agents in a variety of normal and neoplastic cells and have been reported to induce ICAM-1 levels in melanomas, a phenomenon that we confirm in this paper, The effects of retinoids on gene expression usually involve the binding of specific retinoic acid receptor trans-acting factors (RARs) with their ligands, which then interact with specific target sites, the retinoic acid responsive elements (RAREs) present in the promoters of responsive genes, In the case of ICAM-1, we have cloned and analyzed the proximal regulatory region of the human gene, We show that the ICAM-1 promoter is RA-inducible, that it contains a putative consensus RARE (GGGTCATCGCCCTGCC), which binds in vitro RAR alpha complemented with RXRs, and that mutation of the RARE abrogates promoter responsiveness to RA, These studies allow ICAM-1 to be added to the list of genes transcriptionally activated by RA acting through an RARE element. (C) 1995 Academic Press,Inc.