Transgenic Expression of the Helicobacter pylori Virulence Factor CagA Promotes Apoptosis or Tumorigenesis through JNK Activation in Drosophila

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. © 2012 wandle,guillemin.