Stomach-specific c-Myc overexpression drives gastric adenoma in mice through AKT/mammalian target of rapamycin signaling

Gastric cancer (GC) is one of the most common malignant cancers in the world. c-Myc, a well-known oncogene, is commonly amplified in many cancers, including GC. However, it is still not completely understood how c-Myc functions in GC. Here, we generated a stomach-specific c-Myc transgenic mouse model to investigate its role in GC. We found that overexpression of c-Myc in Atp4b(+) gastric parietal cells could induce gastric adenoma in mice. Mechanistically, c-Myc promoted tumorigenesis through the AKT/ mammalian target of rapamycin (mTOR) pathway. Furthermore, AKT inhibitor (MK-2206) or mTOR inhibitor (rapamycin) inhibited the proliferation of c-Myc overexpressing GC cell lines and the initiation of gastric tumorigenesis in c-Myc transgenic mice. Thus, our findings highlight that gastric tumorigenesis can be induced by c-Myc overexpression through activation of the AKT/mTOR pathway.