title: The flt-1 promoter for transcriptional targeting of teratocarcinoma.
abstract: Flt-1, a receptor for vascular endothelial growth factor, is known to display dysregulated expression in both tumor vasculature and tumor cells per se, suggesting that the flt-1 promoter might be a useful candidate to achieve tumor-specific transgene expression. In addition, adenoviral vectors containing transgenes under the control of the flt-1 promoter achieve very low levels of expression in the normal liver, the major organ responsible for blood clearance of adenoviruses and inadvertent transgene-related toxicity. Thus, we assessed the ability of adenoviral vectors containing the flt-1 promoter to achieve transgene expression in a range of gynecological and breast tumor lines. High transgene expression levels were detected in teratocarcinoma lines, correlating with levels of flt-1 mRNA. These results suggest that the flt-1 promoter could be useful for transcriptionally targeted gene expression to teratocarcinoma, and that evaluation in other flt-1-positive tumors is warranted.
authors.affiliation: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Gerd J
authors.initials: GJ
authors.lastname: Bauerschmitz
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Nettelbeck
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
mesh_terms: D000818:Animals; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D018995:Myosin Heavy Chains; D024501:Nonmuscle Myosin Type IIB; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018243:Teratocarcinoma / Q000628:therapy*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C501162:FLT1 protein, human; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains