We hypothesize that TNF functions to reduce tumor initiation resulting in the presence of CagA protein in gastric epithelial cells through a few mechanisms, but that the atmosphere developed by prolonged infection with H. pylori and the emergence of oncogenic mutations with time cause TNF to advertise development of gastric PF299804 molecular weight cancer. . JNK has been shown to have both professional tumorigenic and cyst suppressor functions in different cell types and organs, because it was first discovered. Studies in Drosophila have helped highlight the contexts where JNK activation functions to market tumor progression, specifically in the presence of oncogenic Ras. Recently, JNK was shown to be necessary for activated KRas induced lung tumor formation in mice, suggesting a conserved function of JNK activation in cooperating with activated Ras to market tumorigenesis in mammals. A possible role for JNK pathway activation has additionally been explored Gene expression in mammalian gastric cancer. . Activation of JNK signaling is detected in human gastric cancer samples, and mice lacking JNK1 exhibit a reduction in apoptosis and an attenuation of gastric tumefaction growth induced by the chemical carcinogen Nmethyl N nitrosourea. A role for H. pylori within the context of mammalian gastric cancers induced by cooperation between JNK and Ras signaling has not been investigated. Our finding that CagA expression can induce JNK dependent apoptosis in a polarized epithelium is interesting with respect to data indicating that JNK signaling has developed as a cell editing procedure to get rid of aberrant cells from inside an epithelium. Activation Lonafarnib solubility of JNK signaling can represent a host response directed at eliminating cells containing CagA protein from your gastric epithelium. . Similarly, P. As a bunch defense mechanism aeruginosa mediated activation of JNK signaling in the intestinal epithelium of Drosophila can induce epithelial restoration. Nevertheless, this method may become pathogenic and result in dramatic overproliferation of intestinal cells in animals harboring oncogenic Ras mutations. In H. pylori infection, that may persist for quite some time before the development of gastric cancer, JNK mediated apoptosis could be a powerful system to restrict pathogenic effects on the gastric epithelium. However, this technique of tissue editing can also increase cell turn-over, causing accumulation of genetic variations in host cells. Our data show that acquisition of an oncogenic mutation in host epithelial cells encountering CagA mediated JNK pathway activation can promote tumefaction progression, indicating that this possible host defense strategy can become tumorigenic in a few genetic contexts. Transgenic expression of CagA was recently found to cause neoplastic transformation in a mouse model, giving data for CagAs role as a bacterial oncoprotein in mammals. The low incidence and late development of gastro-intestinal tumors in these mice was attributed to lower expression of CagA in the surviving animals, as larger expression was assumed to be life-threatening during embryogenesis.