KDR promoter can transcriptionally target cytosine deaminase suicide gene to cancer cells of nonendothelial origin.
The KDR/flk-1 gene promoter is considered to be endothelial cell-specific. We show its activity in two cancer cell lines of non-endothelial origin: in murine L1 sarcoma and OVP-10 human ovarian carcinoma cell lines. KDR promoter-driven cytosine deaminase gene can be efficiently expressed in these cells leading to sensitization to 5-fluorocytosine, as demonstrated both in vitro and in vivo. Our results indicated that KDR promoter activity is not endothelial cell-exclusive and that this promoter can also be used to obtain specific expression of therapeutic genes in certain cancer cells.
Szary
J
J
Department of Molecular Biology, Center of Oncology, Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland.
Kalita
K
K
Przybyszewska
M
M
Dus
D
D
Kieda
C
C
Janik
P
P
Szala
S
S
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D043525:Cytosine Deaminase; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology; D005260:Female; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase