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KMID : 0624620090420040217
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BMB Reports
2009 Volume.42 No. 4 p.217 ~ p.222
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Induction of cancer cell-specific death via MMP2 promoterdependent Bax expression
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Seo Eun-Jeong
Kim Se-Woon
Jho Eek-Hoon
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Abstract
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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 rtTA2S-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 rtTA2S-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.
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KEYWORD
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Cancer gene therapy, Lentivirus, MMP-2 promoter, Proapoptotic gene, Tet-On inducible system
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