2.50
Hdl Handle:
http://hdl.handle.net/10033/229672
Title:
Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.
Authors:
Leschner, Sara; Deyneko, Igor V; Lienenklaus, Stefan; Wolf, Kathrin; Bloecker, Helmut; Bumann, Dirk; Loessner, Holger; Weiss, Siegfried
Abstract:
Conventional cancer therapies are often limited in effectiveness and exhibit strong side effects. Therefore, alternative therapeutic strategies are demanded. The employment of tumor-colonizing bacteria that exert anticancer effects is such a novel approach that attracts increasing attention. For instance, Salmonella enterica serovar Typhimurium has been used in many animal tumor models as well as in first clinical studies. These bacteria exhibit inherent tumoricidal effects. In addition, they can be used to deliver therapeutic agents. However, bacterial expression has to be restricted to the tumor to prevent toxic substances from harming healthy tissue. Therefore, we screened an S. Typhimurium promoter-trap library to identify promoters that exclusively drive gene expression in the cancerous tissue. Twelve elements could be detected that show reporter gene expression in tumors but not in spleen and liver. In addition, a DNA motif was identified that appears to be necessary for tumor specificity. Now, such tumor-specific promoters can be used to safely express therapeutic proteins by tumor-colonizing S. Typhimurium directly in the neoplasia.
Affiliation:
Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. sara.leschner@helmholtz-hzi.de
Citation:
Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic. 2012, 40 (7):2984-94 Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
Apr-2012
URI:
http://hdl.handle.net/10033/229672
DOI:
10.1093/nar/gkr1041
PubMed ID:
22140114
Type:
Article
Language:
en
ISSN:
1362-4962
Appears in Collections:
Publications of RG Molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorLeschner, Saraen_GB
dc.contributor.authorDeyneko, Igor Ven_GB
dc.contributor.authorLienenklaus, Stefanen_GB
dc.contributor.authorWolf, Kathrinen_GB
dc.contributor.authorBloecker, Helmuten_GB
dc.contributor.authorBumann, Dirken_GB
dc.contributor.authorLoessner, Holgeren_GB
dc.contributor.authorWeiss, Siegfrieden_GB
dc.date.accessioned2012-06-19T12:39:17Z-
dc.date.available2012-06-19T12:39:17Z-
dc.date.issued2012-04-
dc.identifier.citationIdentification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic. 2012, 40 (7):2984-94 Nucleic Acids Res.en_GB
dc.identifier.issn1362-4962-
dc.identifier.pmid22140114-
dc.identifier.doi10.1093/nar/gkr1041-
dc.identifier.urihttp://hdl.handle.net/10033/229672-
dc.description.abstractConventional cancer therapies are often limited in effectiveness and exhibit strong side effects. Therefore, alternative therapeutic strategies are demanded. The employment of tumor-colonizing bacteria that exert anticancer effects is such a novel approach that attracts increasing attention. For instance, Salmonella enterica serovar Typhimurium has been used in many animal tumor models as well as in first clinical studies. These bacteria exhibit inherent tumoricidal effects. In addition, they can be used to deliver therapeutic agents. However, bacterial expression has to be restricted to the tumor to prevent toxic substances from harming healthy tissue. Therefore, we screened an S. Typhimurium promoter-trap library to identify promoters that exclusively drive gene expression in the cancerous tissue. Twelve elements could be detected that show reporter gene expression in tumors but not in spleen and liver. In addition, a DNA motif was identified that appears to be necessary for tumor specificity. Now, such tumor-specific promoters can be used to safely express therapeutic proteins by tumor-colonizing S. Typhimurium directly in the neoplasia.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Nucleic acids researchen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshCell Hypoxiaen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGene Expression Regulation, Bacterialen_GB
dc.subject.meshGenes, Reporteren_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred BALB Cen_GB
dc.subject.meshNeoplasms, Experimentalen_GB
dc.subject.meshNucleotide Motifsen_GB
dc.subject.meshPromoter Regions, Geneticen_GB
dc.subject.meshSalmonella typhimuriumen_GB
dc.subject.meshSequence Analysis, DNAen_GB
dc.titleIdentification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.en
dc.typeArticleen
dc.contributor.departmentMolecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. sara.leschner@helmholtz-hzi.deen_GB
dc.identifier.journalNucleic acids researchen_GB

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