title: KRas, ROS and the initiation of pancreatic cancer.
abstract: Oncogenic mutations of KRAS are the most frequent driver mutations in pancreatic cancer. Expression of an oncogenic allele of KRAS leads to metabolic changes and altered cellular signaling that both can increase the production of intracellular reactive oxygen species (ROS). Increases in ROS have been shown to drive the formation and progression of pancreatic precancerous lesions by upregulating survival and growth factor signaling. A key issue for precancerous and cancer cells is to keep ROS at levels where they are beneficial for tumor development and progression, but below the threshold that leads to induction of senescence or cell death. In KRas-driven neoplasia aberrantly increased ROS levels are therefore balanced by an upregulation of antioxidant genes.
authors.affiliation: a Department of Cancer Biology , Mayo Clinic Comprehensive Cancer Center, Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D018450:Disease Progression; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C117307:KRAS protein, human; D017382:Reactive Oxygen Species; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRas; PanIN; ROS; mitochondria; oxidative stress; pancreatic cancer