title: Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence.
abstract: Pancreatic acinar cells of adult mice (≥P60) are resistant to transformation by some of the most robust oncogenic insults including expression of K-Ras oncogenes and loss of p16Ink4a/p19Arf or Trp53 tumor suppressors. Yet, these acinar cells yield pancreatic intraepithelial neoplasias (mPanIN) and ductal adenocarcinomas (mPDAC) if exposed to limited bouts of non-acute pancreatitis, providing they harbor K-Ras oncogenes. Pancreatitis contributes to tumor progression by abrogating the senescence barrier characteristic of low-grade mPanINs. Attenuation of pancreatitis-induced inflammation also accelerates tissue repair and thwarts mPanIN expansion. Patients with chronic pancreatitis display senescent PanINs, providing they have received antiinflammatory drugs. These results support the concept that antiinflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC.
authors.affiliation: Experimental Oncology, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. mcguerra@cnio.es
authors.forename: Carmen
authors.initials: C
authors.lastname: Guerra
authors.forename: Manuel
authors.initials: M
authors.lastname: Collado
authors.forename: Carolina
authors.initials: C
authors.lastname: Navas
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Schuhmacher
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández-Porras
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Justo
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.forename: Mariano
authors.initials: M
authors.lastname: Barbacid
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000209:etiology; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D011905:Genes, ras; D006801:Humans; D051379:Mice; D046790:Pancreas, Exocrine / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000517:prevention & control; D010195:Pancreatitis / Q000150:complications*
chemical_list: D000893:Anti-Inflammatory Agents; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16