Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines.
The DEAD box gene, DDX1, is a putative RNA helicase that is co-amplified with MYCN in a subset of retinoblastoma (RB) and neuroblastoma (NB) tumors and cell lines. Although gene amplification usually involves hundreds to thousands of kilobase pairs of DNA, a number of studies suggest that co-amplified genes are only overexpressed if they provide a selective advantage to the cells in which they are amplified. Here, we further characterize DDX1 by identifying its putative transcription and translation initiation sites. We analyze DDX1 protein levels in MYCN/DDX1-amplified NB and RB cell lines using polyclonal antibodies specific to DDX1 and show that there is a good correlation with DDX1 gene copy number, DDX1 transcript levels, and DDX1 protein levels in all cell lines studied. DDX1 protein is found in both the nucleus and cytoplasm of DDX1-amplified lines but is localized primarily to the nucleus of nonamplified cells. Our results indicate that DDX1 may be involved in either the formation or progression of a subset of NB and RB tumors and suggest that DDX1 normally plays a role in the metabolism of RNAs located in the nucleus of the cell.
Department of Oncology, Cross Cancer Institute and University of Alberta, 11560 University Ave., Edmonton, Alberta T6G1Z2, Canada.
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D001483:Base Sequence; D053487:DEAD-box RNA Helicases; D018076:DNA, Complementary; D006801:Humans; D007106:Immune Sera; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D007106:Immune Sera; D012333:RNA, Messenger; D012316:RNA Nucleotidyltransferases; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases