The epigenetic regulators Bmi1 and Ring1B are differentially regulated in pancreatitis and pancreatic ductal adenocarcinoma
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Le résumé fourni par la source
Chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are associated with major changes in cell differentiation. These changes may be at the basis of the increased risk for PDAC among patients with chronic pancreatitis. Polycomb proteins are epigenetic silencers expressed in adult stem cells; up-regulation of Polycomb proteins has been reported to occur in a variety of solid tumours such as colon and breast cancer. We hypothesized that Polycomb might play a role in preneoplastic states in the pancreas and in tumour development/progression. To test these ideas, we determined the expression of PRC1 complex proteins (Bmi1 and Ring1b) during pancreatic development and in pancreatic tissue from mouse models of disease: acute and chronic pancreatic injury, duct ligation, and in K-Ras(G12V) conditional knock-in and caerulein-treated K-Ras(G12V) mice. The study was extended to human pancreatic tissue samples. To obtain mechanistic insights, Bmi1 expression in cells undergoing in vitro exocrine cell metaplasia and the effects of Bmi1 depletion in an acinar cancer cell line were studied. We found that Bmi1 and Ring1B are expressed in pancreatic exocrine precursor cells during early development and in ductal and islet cells-but not acinar cells-in the adult pancreas. Bmi1 expression was induced in acinar cells during acute injury, in acinar-ductal metaplastic lesions, as well as in pancreatic intraepithelial neoplasia (PanIN) and PDAC. In contrast, Ring1B expression was only significantly and persistently up-regulated in high-grade PanINs and in PDAC. Bmi1 knockdown in cultured acinar tumour cells led to changes in the expression of various digestive enzymes. Our results suggest that Bmi1 and Ring1B are modulated in pancreatic diseases and could contribute differently to tumour development.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The epigenetic regulators Bmi1 and Ring1B are differentially regulated in pancreatitis and pancreatic ductal adenocarcinoma
- Date Crossref
- 07/07/2009
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Barcelona Biomedical Research Park pays non établi dans la noticeStructure de recherche
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Hospital Del Mar Programa de Recerca en Càncer pays non établi dans la noticeÉtablissement de santé
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Municipal Institute for Medical Research pays non établi dans la noticeÉtablissement de santé
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Spanish National Cancer Research Centre pays non établi dans la noticeStructure de recherche
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Universitat Autònoma de Barcelona pays non établi dans la noticeUniversité ou école supérieure
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Universitat Pompeu Fabra pays non établi dans la noticeUniversité ou école supérieure
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Institut Municipal d'Investigació Mèdica pays non établi dans la noticeStructure de recherche
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These authors contributed equally to this work pays non établi dans la noticeInstitution
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Programa de Oncología Molecular pays non établi dans la noticeInstitution
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. Institut de Recerca Hospital Universitari Vall d'Hebron Grup de Recerca en Fisiologia y Fisiopatologia Digestiva pays non établi dans la noticeStructure de recherche
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Hospital Universitari del Mar Departament de Patología pays non établi dans la noticeÉtablissement de santé
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Departament de Ciències Experimentals i de la Salut pays non établi dans la noticeInstitution
Barcelona Biomedical Research Park, Programa de Recerca en Càncer — Hospital Del Mar et Municipal Institute for Medical Research, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.