Induction of cancer cell-specific death via MMP2 promoterdependent Bax expression

Controlled gene expression in specific cells is a valuable tool for gene therapy. We attempted to determine whether the lentivirus-mediated Tet-On inducible system could be applied to cancer gene therapy. In order to select the genes that induce cancer cell death, we compared the ability of the know...

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Bibliographic Details
Published in:BMB reports 2009-04, Vol.42 (4), p.217-222
Main Authors: Seo, Eunjeong, Kim, Sewoon, Jho, Eek-hoon
Format: Article
Language:English
Subjects:
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - physiology
BH3 Interacting Domain Death Agonist Protein - genetics
BH3 Interacting Domain Death Agonist Protein - physiology
Caco-2 Cells
Cell Death - genetics
Cell Death - physiology
Cell Line
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Cyclin-Dependent Kinase Inhibitor p21 - physiology
Gene Expression Regulation, Neoplastic
Genetic Vectors - genetics
HeLa Cells
Humans
In Situ Nick-End Labeling
Lentivirus - genetics
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 2 - physiology
Promoter Regions, Genetic - genetics
Promoter Regions, Genetic - physiology
Reverse Transcriptase Polymerase Chain Reaction
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Summary:Controlled gene expression in specific cells is a valuable tool for gene therapy. We attempted to determine whether the lentivirus-mediated Tet-On inducible system could be applied to cancer gene therapy. In order to select the genes that induce cancer cell death, we compared the ability of the known pro-apoptotreic genes, Bax and tBid, and a cell cycle inhibitor, p21cip1/waf1, and determined that Bax was the most effective. For the cancer cell-specific expression of rtTA2(S)-M2, we tested the matrix metalloproteinase-2 (MMP-2) promoter and determined that it is highly expressed in cancer cell lines, including SNU475 cells. The co-transduction of two lentiviruses that contain sequences for TRE-Bax and rtTA2(S)-M2, the expression of which is controlled by the MMP-2 promoter, resulted in the specific cell death of SNU475, whereas other cells with low MMP-2 expression did not evidence significant cell death. Our data indicate that the lentivirus-mediated Tet-On system using the cancer-specific promoter is applicable for cancer gene therapy.
ISSN:1976-6696
DOI:10.5483/BMBRep.2009.42.4.217