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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Proliferation, DNA Methylation, DNA Mutational Analysis, DNA, Mitochondrial, Down-Regulation, Epithelium, Female, Gene Expression Regulation, Neoplastic, Humans, Ki-67 Antigen, Male, Metaplasia, Mice, Mice, Inbred C57BL, Mice, Knockout, Mucin 5AC, Mucin-6, Mutation, Neoplasms, Cystic, Mucinous, and Serous, Pancreas, Pancreatic Ducts, Pancreatic Neoplasms, Pancreatitis, Chronic, Promoter Regions, Genetic, Smad4 Protein, Trefoil Factor-1, Trefoil Factor-2.
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Does loss of Trefoil Factor 2 From Pancreatic Duct Glands promote Formation of Intraductal Papillary Mucinous Neoplasms in Mice? Context: Little is known about the origin of pancreatic intraductal papillary mucinous neoplasms (IPMN). Pancreatic duct glands (PDGs) are gland-like outpouches budding off the main pancreatic ducts that function as a progenitor niche for the ductal epithelium; they express gastric mucins and have characteristics of side-branch IPMNs. We investigated whether PDGs are a precursor compartment for IPMNs and the role of Trefoil factor family 2 (TFF2)-a protein expressed by PDGs and the gastric mucosa that are involved in epithelial repair and tumor suppression. We obtained pancreatectomy specimens from 20 patients with chronic pancreatitis, 13 with low-grade side-branch IPMNs, and 15 patients with PDAC; histologically normal pancreata were used as controls (n = 18). Samples were analyzed by immunohistochemistry to detect TFF1 and TFF2 and cell proliferation. We performed mitochondrial DNA mutational mapping studies to determine the cell lineage and fate of PDG cells. Pdx1-Cre;LSL-KRAS Histologic analysis of human samples revealed gastric-type IPMN to comprise 2 molecularly distinct layers: a basal crypt segment that expressed TFF2 and overlying papillary projections. Proliferation occurred predominantly in the PDG-containing basal segments. Mitochondrial mutation mapping revealed a 97% match between the profiles of proliferating PDG cells and their overlying nonproliferative IPMN cells. In contrast to KC mice, 2-month-old KC/Tff2
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In histologic analyses of human IPMNs, we found PDGs to form the basal segment and possibly serve as a progenitor compartment. TFF2 has tumor-suppressor activity in the mouse pancreas and prevents formation of mucinous neoplasms. Final Decision: yes