title: Selective alteration of gene expression in response to natural and synthetic retinoids.
abstract: BACKGROUND
  Retinoids are very potent inducers of cellular differentiation and apoptosis, and are efficient anti-tumoral agents. Synthetic retinoids are designed to restrict their toxicity and side effects, mostly by increasing their selectivity toward each isotype of retinoic acids receptors (RARalpha,beta, gamma and RXRalpha, beta, gamma). We however previously showed that retinoids displayed very different abilities to activate retinoid-inducible reporter genes, and that these differential properties were correlated to the ability of a given ligand to promote SRC-1 recruitment by DNA-bound RXR:RAR heterodimers. This suggested that gene-selective modulation could be achieved by structurally distinct retinoids.
  
  
  RESULTS
  Using the differential display mRNA technique, we identified several genes on the basis of their differential induction by natural or synthetic retinoids in human cervix adenocarcinoma cells. Furthermore, this differential ability to regulate promoter activities was also observed in murine P19 cells for the RARbeta2 and CRABPII gene, showing conclusively that retinoid structure has a dramatic impact on the regulation of endogenous genes.
  
  
  CONCLUSIONS
  Our findings therefore show that some degree of selective induction or repression of gene expression may be achieved when using appropriately designed ligands for retinoic acid receptors, extending the concept of selective modulators from estrogen and peroxisome proliferator activated receptors to the class of retinoid receptors.
authors.affiliation: INSERM U 459 and Ligue nationale contre le Cancer, Faculté de Médecine Henri Warembourg, 1, place de Verdun, 59045 Lille cedex, France. brand@lille.inserm.fr
authors.forename: Céline
authors.initials: C
authors.lastname: Brand
authors.forename: Pascaline
authors.initials: P
authors.lastname: Ségard
authors.forename: Pascal
authors.initials: P
authors.lastname: Plouvier
authors.forename: Pierre
authors.initials: P
authors.lastname: Formstecher
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Danzé
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C000607071:RARA protein, human; D012333:RNA, Messenger; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; C082928:retinoic acid binding protein II, cellular; C082925:retinoic acid receptor beta