title: RARα mediates all-trans-retinoic acid-induced VEGF-C, VEGF-D, and VEGFR3 expression in lung cancer cells.
abstract: The regulation of vascular endothelial growth factors C (VEGF-C) and D (VEGF-D), and their receptor VEGFR3 gene and protein expression by all-trans-retinoic acid (atRA) in A549 lung cancer cells, was investigated. We showed that atRA treatment increased VEGF-C, VEGF-D, and VEGFR3 protein and mRNA contents in dose-dependent manner. atRA-mediated increase of both ligands and receptor expression correlated with the elevated level of retinoic acid receptor α (RARα) expression, while the level of another atRA receptor, peroxisome proliferator-activated receptor β/δ (PPARβ/δ), was decreased. We demonstrated that the classical counterpart of RARα, retinoid X receptor α (RXRα), was down-regulated in both cytoplasm and nucleus of A549 cells upon atRA addition. On the contrary, the nuclear quantity of another possible RARα counterpart, transcription factor Sp1, was increased after atRA treatment.
authors.affiliation: Laboratory of Tumor Cell Genetics, Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, 115478, Russia.
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Kalitin
authors.affiliation: Laboratory of Tumor Cell Genetics, Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, 115478, Russia.
authors.forename: Aida F
authors.initials: AF
authors.lastname: Karamysheva
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000072482:Retinoic Acid Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000072482:Retinoic Acid Receptor alpha; D016329:Sp1 Transcription Factor; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D014212:Tretinoin; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: All-trans-retinoic acid; RARα; VEGF-C; VEGF-D; VEGFR3