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 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.
Seo
Eunjeong
E
Department of Life Science, The University of Seoul, Seoul, Korea.
Kim
Sewoon
S
Jho
Eek-hoon
EH
D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000502:physiology; D018938:Caco-2 Cells; D016923:Cell Death / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D016086:Lentivirus / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000502:physiology*
D051023:BH3 Interacting Domain Death Agonist Protein; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051028:bcl-2-Associated X Protein; D020778:Matrix Metalloproteinase 2