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

Eun-Jeong Seo, Se-Woon Kim, Eek-hoon Jho
2009 BMB Reports  
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
more » ... atrix 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. [BMB reports 2009; 42(4): 217-222]
doi:10.5483/bmbrep.2009.42.4.217 pmid:19403045 fatcat:mxvezh6rgjexniwekv2gawnr7m