title: Regression of solid tumors by induction of MazF, a bacterial mRNA endoribonuclease.
abstract: MazF from Escherichia coli is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. Its induction in mammalian cells has been shown to cause programmed cell death. Here we explored if a bacterial MazF-MazE toxin-antitoxin system can be used for gene therapy. For this, we first constructed a tetracycline-inducible MazF expression system in human embryonic kidney cells (T-Rex 293-mazF). Solid tumors were formed by injecting T-Rex 293-mazF cells into nude mice. All 8 mice injected with the cells developed solid tumors, which regressed upon induction of MazF. In 4 mice, tumors completely regressed, while in the remaining 4 mice, tumors reappeared after apparent significant regression, which was found to be due to the lack of presence of functional MazF. Notably, the MazF-mediated regression of the tumors was counteracted by the expression of its cognate antitoxin MazE. These results indicate that a bacterial MazF-MazE toxin-antitoxin system may have potential to be used as a therapeutic tool.
authors.affiliation: Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Piscataway, N.J., USA.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimazu
authors.forename: Oleg
authors.initials: O
authors.lastname: Mirochnitchenko
authors.forename: Sangita
authors.initials: S
authors.lastname: Phadtare
authors.forename: Masayori
authors.initials: M
authors.lastname: Inouye
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422954:MazE protein, E coli; C422955:MazF protein, E coli; D011994:Recombinant Proteins; D004722:Endoribonucleases