title: Senescence in pancreatic carcinogenesis: from signalling to chromatin remodelling and epigenetics.
abstract: Mutational activation of K-Ras is a key genetic event involved in the initiation of pancreatic carcinogenesis. However, K-Ras generally fails to transform precursor lesions into invasive cancers due to activation of powerful fail-safe programmes that counteract transformation and growth. The importance of cellular senescence, a permanent cell growth arrest, is increasingly being recognised as a critical fail-safe programme in pancreatic carcinogenesis. Emerging evidence suggests that oncogene-induced senescence requires transcriptional induction of the CDKN2A gene locus as well as comprehensive chromatin modifications involved in epigenetic silencing of pro-proliferative genes. Moreover, recent work in pancreatic cancer mouse models proposes that inactivation of the CDKN2A tumour suppressor locus is the molecular switch required for senescence evasion and unleashed K-Ras driven malignant transformation in the pancreas.
authors: Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University of Marburg, Marburg, Germany.
authors: Shiv K
authors: SK
authors: Singh
authors: Volker
authors: V
authors: Ellenrieder
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D016922:Cellular Senescence / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D019942:Genes, p16; D011905:Genes, ras; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction