The flt-1 promoter for transcriptional targeting of teratocarcinoma.
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.
Bauerschmitz
Gerd J
GJ
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Nettelbeck
Dirk M
DM
Kanerva
Anna
A
Baker
Andrew H
AH
Hemminki
Akseli
A
Reynolds
Paul N
PN
Curiel
David T
DT
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
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