Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia.

Détails

ID Serval
serval:BIB_13E70682D4D9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia.
Périodique
Gut
Auteur⸱e⸱s
Prévot P.P., Simion A., Grimont A., Colletti M., Khalaileh A., Van den Steen G., Sempoux C., Xu X., Roelants V., Hald J., Bertrand L., Heimberg H., Konieczny S.F., Dor Y., Lemaigre F.P., Jacquemin P.
ISSN
1468-3288 (Electronic)
ISSN-L
0017-5749
Statut éditorial
Publié
Date de publication
2012
Volume
61
Numéro
12
Pages
1723-1732
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
OBJECTIVE: Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). The transcriptional regulators required to initiate ADM are unknown, but need to be identified to characterise the regulatory networks that drive ADM. In this study, the role of the ductal transcription factors hepatocyte nuclear factor 6 (HNF6, also known as Onecut1) and SRY-related HMG box factor 9 (Sox9) in ADM was investigated.
DESIGN: Expression of HNF6 and Sox9 was measured by immunostaining in normal and diseased human pancreas. The function of the factors was tested in cultured cells and in mouse models of ADM by a combination of gain and loss of function experiments.
RESULTS: Expression of HNF6 and Sox9 was ectopically induced in acinar cells in human ADM as well as in mouse models of ADM. HNF6 and, to a lesser extent, Sox9 were required for repression of acinar genes, for modulation of ADM-associated changes in cell polarity and for activation of ductal genes in metaplastic acinar cells.
CONCLUSIONS: HNF6 and Sox9 are new biomarkers of ADM and constitute candidate targets for preventive treatment in cases when ADM may lead to cancer. This work also shows that ectopic activation of transcription factors may underlie metaplastic processes occurring in other organs.
Mots-clé
Acinar Cells/metabolism, Acinar Cells/pathology, Animals, Blotting, Western, Cell Transformation, Neoplastic/metabolism, Cells, Cultured, Guinea Pigs, Hepatocyte Nuclear Factor 6/metabolism, Humans, Metaplasia, Mice, Models, Animal, Pancreas/metabolism, Pancreas/pathology, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, SOX9 Transcription Factor/metabolism, Tumor Markers, Biological/metabolism
Pubmed
Web of science
Création de la notice
26/01/2015 12:51
Dernière modification de la notice
20/08/2019 13:42
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