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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Induction of cancer cell-specific death via MMP2 promoterdependent Bax expression

  • Seo, Eun-Jeong (Department of Life Science, The University of Seoul) ;
  • Kim, Se-Woon (Department of Life Science, The University of Seoul) ;
  • Jho, Eek-hoon (Department of Life Science, The University of Seoul)
  • Published : 2009.04.30
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Abstract

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.

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References

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