title: Transgenic expression of the Helicobacter pylori virulence factor CagA promotes apoptosis or tumorigenesis through JNK activation in Drosophila.
abstract: Gastric cancer development is strongly correlated with infection by Helicobacter pylori possessing the effector protein CagA. Using a transgenic Drosophila melanogaster model, we show that CagA expression in the simple model epithelium of the larval wing imaginal disc causes dramatic tissue perturbations and apoptosis when CagA-expressing and non-expressing cells are juxtaposed. This cell death phenotype occurs through activation of JNK signaling and is enhanced by loss of the neoplastic tumor suppressors in CagA-expressing cells or loss of the TNF homolog Eiger in wild type neighboring cells. We further explored the effects of CagA-mediated JNK pathway activation on an epithelium in the context of oncogenic Ras activation, using a Drosophila model of metastasis. In this model, CagA expression in epithelial cells enhances the growth and invasion of tumors in a JNK-dependent manner. These data suggest a potential role for CagA-mediated JNK pathway activation in promoting gastric cancer progression.
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA.
authors.forename: Anica M
authors.initials: AM
authors.lastname: Wandler
authors.forename: Karen
authors.initials: K
authors.lastname: Guillemin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D060227:Imaginal Discs / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; C080866:cagA protein, Helicobacter pylori; C464573:egr protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D015689:Oncogene Protein p21(ras)