In vitro evaluation of cancer-specific NF-kappaB-CEA enhancer-promoter system for 5-fluorouracil prodrug gene therapy in colon cancer cell lines.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Armesilla, Angel Luis
Darling, John L.
MetadataShow full item record
AbstractNuclear factor-kappa B (NF-kappaB) is a transcription factor with high transcriptional activity in cancer cells. In this study, we developed a novel enhancer-promoter system, kappaB4-CEA205, in which the basal carcinoembryonic antigen (CEA) promoter sequence (CEA205) was placed downstream of the four tandem-linked NF-kappaB DNA-binding sites (kappaB4). In combination with a kappaB4 enhancer, the transcriptional activity of the CEA promoter was significantly enhanced (three- to eight-fold) in cancer cell lines but not in normal cells. In cancer cell lines, the transcriptional activity of kappaB4-CEA205 was comparable with that of the SV40 promoter. We also constructed vectors in which the thymidine phosphorylase (TP) cDNA was under the control of CEA205, kappaB4, kappaB4-CEA205 and CMV promoters, respectively. TP protein and enzyme activity were detected at comparable levels in kappaB4-CEA205- and CMV-driven TP cDNA-transfected cancer cell lines (H630 and RKO). The kappaB4-TP and CEA205-TP-transfected cell lines, respectively, only demonstrated negligible and low levels of TP protein and enzyme activity. Both CMV- and kappaB4-CEA205-driven TP cDNA transiently transfected cells were 8- to 10-fold sensitised to 5-fluorouracil (5-FU) prodrug, 5'-deoxy-5-fluorouradine (5'-DFUR), in contrast to only 1.5- to 2-fold sensitised by the kappaB4- and CEA205-driven TP cDNA-transfected cells. The bystander killing effect of CMV- and kappaB4-CEA205-driven TP cDNA-transfected cells was comparable. This is the first report that indicates that the NF-kappaB DNA-binding site could be used as a novel cancer-specific enhancer to improve cancer-specific promoter activity in gene-directed enzyme prodrug therapy.
CitationBritish Journal of Cancer, 97(6): 745-754
PublisherNature Publishing Group
JournalBritish Journal of Cancer
- [Transfection of thymidine phosphorylase cDNA with lentiviral vector enhances the anticancer effect of 5'-deoxy-5-fluorouridine on colorectal cancer cell lines HT29 and LS174T].
- Authors: Ye D, Wang Q, Zhang J, Liu Q
- Issue date: 2015 Jan
- [Enhanced anticancer effects of 5'-DFUR on colorectal cancer cell lines SW480 and LOVO by transfection with thymidine phosphorylase cDNA].
- Authors: Liu J, Zhang JM, Gao Q, Wang QW, Ye DJ, Liu Y
- Issue date: 2013 Jul
- Prostate-specific antigen promoter/enhancer driven gene therapy for prostate cancer: construction and testing of a tissue-specific adenovirus vector.
- Authors: Latham JP, Searle PF, Mautner V, James ND
- Issue date: 2000 Jan 15
- Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase.
- Authors: Evrard A, Cuq P, Ciccolini J, Vian L, Cano JP
- Issue date: 1999 Aug
- CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter.
- Authors: Dabrowska A, Szary J, Kowalczuk M, Szala S, Ugorski M
- Issue date: 2004