regulation of gene expression in hepatic cells by the mammalian target of rapamycin (mtor)监管在肝细胞中基因表达的哺乳动物雷帕霉素靶(mtor).pdfVIP

Regulation of Gene Expression in Hepatic Cells by the Mammalian Target of Rapamycin (mTOR) 1 2 3 3 4,5 Rosa H. Jimenez , Ju-Seog Lee , Mirko Francesconi , Gastone Castellani , Nicola Neretti , Jennifer A. 1 5 1 Sanders , John Sedivy , Philip A. Gruppuso * 1 Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, Rhode Island, United States of America, 2 Molecular Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 3 Interdepartmental Center ‘‘L. Galvani’’, Bologna University, Bologna, Italy, 4 Institute for Brain and Neural Systems, Brown University, Providence, Rhode Island, United States of America, 5 Department of Molecular Biology, Cell Biology and Biochemistry and Center for Genomics and Proteomics, Brown University, Providence, Rhode Island, United States of America Abstract Background: We investigated mTOR regulation of gene expression by studying rapamycin effect in two hepatic cell lines, the non-tumorigenic WB-F344 cells and the tumorigenic WB311 cells. The latter are resistant to the growth inhibitory effects of rapamycin, thus providing us with an opportunity to study the gene expression effects of rapamycin without confounding effects on cell proliferation. Methodology/Principal Findings: The hepatic cells were exposed to rapamycin for 24 hr. Microarray analysis on total RNA preparations identified genes that were affected by rapamycin in both cell lines and, therefore, modulated independent of growth arrest. Further studies showed that the promoter regions of these genes included E-box-containing transcription factor bi