Conditional deletion of p53 and Rb in the renin-expressing compartment of the pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine carcinoma.

摘要: Efforts to model human pancreatic neuroendocrine tumors (PanNETs) in animals have been moderately successful, with minimal evidence for glucagonomas or metastatic spread. The renin gene, although classically associated expression the kidney, is also expressed many other extrarenal tissues including pancreas. To induce tumorigenesis within rennin-specific tissues, floxed alleles of p53 and Rb were selectively abrogated using Cre-recombinase driven by promoter. primary neoplasm generated a highly islet cell carcinoma Lineage tracing identifies descendants renin-expressing cells as alpha despite lack active mature Both express high levels glucagon; furthermore, an increased level glucagon found serum, identifying cancer functional glucagonoma. This new penetrant exhibits robust frequency metastases lymph nodes liver, mimicking disease, provides useful platform better understanding endocrine differentiation development, well carcinogenesis. use fluorescent reporters lineage contributing disease initiation progression unique opportunity dissect timeline examining mechanisms process, recovering cooperating mutations that are necessary disease.