Premium
Regulation of intercellular adhesion molecule‐1 expression by retinoic acid: Analysis of the 5′ regulatory region of the gene
Author(s) -
Aoudjit Fawzi,
Bosse Marc,
Stratowa Christian,
Voraberger Günter,
Audette Marie
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580416
Subject(s) - retinoic acid , retinoic acid receptor , retinoic acid receptor beta , microbiology and biotechnology , reporter gene , transfection , retinoid x receptor gamma , biology , retinoic acid receptor alpha , retinoic acid inducible orphan g protein coupled receptor , retinoic acid receptor gamma , gene expression , tretinoin , biochemistry , gene
Human intercellular adhesion molecule‐1 (ICAM‐1), a specific ligand for the lymphocyte‐function‐associated antigen‐1, plays an important role in immune responses. ICAM‐I expression is regulated by various proinflammatory cytokines, by PMA, and by retinoic acid. In this study, we have investigated the mechanisms of transcriptional control involved in the stimulation of ICAM‐I gene expression by retinoic acid in SK‐N‐SH cells. Northern‐blot analysis demonstrated that ICAM‐I mRNA is maximally induced at 24 hr, suggesting that it is not an early‐response gene with respect to retinoic‐acid responsiveness, whereas the retinoic acid receptorβ mRNA level was maximal 12 hr following retinoic acid treatment. To analyze the 5′‐regulatory region of the ICAM‐I gene, an EcoRI/Sall fragment spanning the first 1.3 kb upstream of the translational start site was used to direct the expression of a linked luciferase reporter gene in transient transaction assays in SK‐N‐SH cells. A 24‐hr treatment of transfected cells with 10μ retinoic acid resulted in a 10‐ to 13‐fold increase in luciferase activity compared with untreated cells. Deletion mutant analysis revealed that a region located between ‐393 and ‐ 176 bp from the translational start site is critical for retinoic acid stimulation of luciferase activity. This region harbors a consensus sequence for a retinoic‐acid‐responsive element (RARE) homologous to the element found upstream of the alcohol dehydrogenase‐3 gene. Co‐transfection of expression vectors encoding the retinoic acid receptor‐α, ‐β, or ‐γ, with reporter plasmids harboring the putative RARE, confirmed that the ICAM‐I gene is regulated by retinoic acid in a retinoic acid receptor‐dependent fashion.