retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cellsretinoid-induced立即早期肿瘤抑制基因的表达和活动在血管平滑肌细胞.pdfVIP

Retinoid-Induced Expression and Activity of an Immediate Early Tumor Suppressor Gene in Vascular Smooth Muscle Cells 1 1 1 1 1 1 Jeffrey W. Streb , Xiaochun Long , Ting-Hein Lee , Qiang Sun , Chad M. Kitchen , Mary A. Georger , 1 3 4 5 1,2 Orazio J. Slivano , William S. Blaner , Daniel W. Carr , Irwin H. Gelman , Joseph M. Miano * 1 Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, 2 Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, 3 Department of Medicine, Columbia University, New York, New York, United States of America, 4 Portland Veterans Affairs Medical Center, Portland, Oregon, United States of America, 5 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, United States of America Abstract Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE) located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12b) in cultured smooth muscle cells (SMC) as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12b is a retinoid-induced, immediate- early gene. Akap12b promot