2026-08-05T11:41:47Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/201992024-11-29T19:41:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Martínez-Romero, Carles
author
Rooman, Ilse
author
Skoudy, Anouchka
author
Guerra, Carmen
author
Molero, Xavier
author
González, Ana
author
Iglesias, Mar
author
Lobato, Tania
author
Bosch, Almudena
author
Barbacid, Mariano
author
Real Arribas, Francisco
author
Hernández-Muñoz, Inmaculada
funder
Instituto de Salud Carlos III
funder
Biomed Programme
funder
Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
funder
European Union (EU)
2024-07-08T10:35:58Z
2024-07-08T10:35:58Z
2009-10
J Pathol 2019;219(2):205-213
10.1002/path.2585
1096-9896
The Journal of pathology
19585519
http://hdl.handle.net/20.500.12105/20199
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.
eng
The epigenetic regulators Bmi1 and Ring1B are differentially regulated in pancreatitis and pancreatic ductal adenocarcinoma.
journal article
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The JoThe epigeneticregulatorsBmi1andRing1B_2009.pdf
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The JoThe epigeneticregulatorsBmi1andRing1B_2009.pdf.txt