title: Differential regulation of constitutive and retinoic acid-induced galectin-1 gene transcription in murine embryonal carcinoma and myoblastic cells.
abstract: Galectin-1 (gal-1), a galactoside-binding lectin, is found in many vertebrate tissues and its expression is regulated during development. We had found that gal-1 expression is increased in F9 murine embryonal carcinoma cells concurrently with induction of differentiation by all-trans retinoic acid (RA). In contrast, gal-1 expression was constitutively high in murine myoblastic C2C12 cells. Therefore, we used these two cell types as models to begin to understand the mechanisms underlying constitutive and RA-induced gal-1 expression. We transfected transiently into F9 cells a series of reporter constructs containing different deletions of the 5' upstream region of the gal-1 gene promoter placed upstream of the chloramphenicol acetyltransferase reporter cDNA and evaluated the activation of transcription by RA treatment. The results indicate that the induction of gal-1 by RA is regulated at least partially at the level of transcription. A strong RA responsiveness region was found within the sequence from -1578 to -1448 upstream of the transcription start site (+1). In contrast, the high constitutive gal-1 expression in C2C12 cells appeared to be mediated by a sequence within the promoter region from -62 to +1, which contains an Sp1 consensus sequence. A gel electrophoretic mobility shift assay indicated that the transcription factor SP1 bound to the gal-1 Sp1 site and mutagenesis of this Sp1 site abolished both the binding of nuclear proteins to the mutated Sp1 site and the high constitutive expression of the gal-1 gene. The results demonstrate that gal-1 expression is cell type-specific and suggest that different factors regulate constitutive and RA-induced gal-1 expression.
authors.affiliation: Department of Urology, College of Medicine, University of Tennessee, Coleman Building, H221, 956 Court Avenue, Memphis, TN, USA. ylu@utmem1.utmem.edu
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: D
authors.initials: D
authors.lastname: Lotan
authors.forename: R
authors.initials: R
authors.lastname: Lotan
mesh_terms: D000818:Animals; D001665:Binding Sites; D018236:Carcinoma, Embryonal; D002460:Cell Line; D037483:Galectin 1; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006388:Hemagglutinins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D037483:Galectin 1; D006388:Hemagglutinins; D018168:Receptors, Retinoic Acid; D016329:Sp1 Transcription Factor; C082925:retinoic acid receptor beta; D014212:Tretinoin