Gastroenterology 2018 04 15;154(5):1494-1508.e13. Epub 2017 Dec 15.
Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York. Electronic address:
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J Pathol 2012 Apr 17;226(5):723-34. Epub 2012 Jan 17.
Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a ductal phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring a mutated kras under the control of a pancreas-specific promoter that ductal cancer might arise in the centroacinar-acinar region, possibly through a process of acinar-ductal metaplasia (ADM). In order to further elucidate this model of PDAC development, an extensive expression analysis and molecular characterization of the putative and already established (PanIN) precursor lesions were performed in the Kras(G12D/+) ; Ptf1a-Cre(ex1/+) mouse model and in human tissues, focusing on lineage markers, developmental pathways, cell cycle regulators, apomucins, and stromal activation markers. Read More
Gastroenterology 2014 Jan 30;146(1):233-44.e5. Epub 2013 Aug 30.
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida. Electronic address:
Background & Aims: Metaplasias often have characteristics of developmentally related tissues. Pancreatic metaplastic ducts are usually associated with pancreatitis and pancreatic ductal adenocarcinoma. The tuft cell is a chemosensory cell that responds to signals in the extracellular environment via effector molecules. Read More
Gastroenterology 2015 May 23;148(5):1024-1034.e9. Epub 2015 Jan 23.
Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. Electronic address:
Background & Aims: Oncogenic mutations in KRAS contribute to the development of pancreatic ductal adenocarcinoma, but are not sufficient to initiate carcinogenesis. Secondary events, such as inflammation-induced signaling via the epidermal growth factor receptor (EGFR) and expression of the SOX9 gene, are required for tumor formation. Herein we sought to identify the mechanisms that link EGFR signaling with activation of SOX9 during acinar-ductal metaplasia, a transdifferentiation process that precedes pancreatic carcinogenesis. Read More
Gastroenterology 2016 Jan 25;150(1):218-228.e12. Epub 2015 Sep 25.
The Department of Pathology, Columbia University Medical Center, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Department of Otolaryngology and Head and Neck Surgery, Columbia University Medical Center, New York, New York. Electronic address:
Background & Aims: Activin, a member of the transforming growth factor-β (TGFB) family, might be involved in pancreatic tumorigenesis, similar to other members of the TGFB family. Human pancreatic ductal adenocarcinomas contain somatic mutations in the activin A receptor type IB (ACVR1B) gene, indicating that ACVR1B could be a suppressor of pancreatic tumorigenesis.
Methods: We disrupted Acvr1b specifically in pancreata of mice (Acvr1b(flox/flox);Pdx1-Cre mice) and crossed them with LSL-KRAS(G12D) mice, which express an activated form of KRAS and develop spontaneous pancreatic tumors. Read More