title: Snail1 is required for the maintenance of the pancreatic acinar phenotype.
abstract: The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue. Snail1 expression was not detected in the epithelium but was in pancreatic mesenchymal cells (PMCs). Snail1 ablation in cultured PMCs downregulated the expression of several β-catenin/Tcf-4 target genes, modified the secretome of these cells and decreased their ability to maintain acinar markers in cultured pancreas cells. Finally, Snail1 deficiency modified the phenotype of pancreatic tumors generated in transgenic mice expressing c-myc under the control of the elastase promoter. Specifically, Snail1 depletion did not significantly alter the size of the tumors but accelerated acinar-ductal metaplasia. These results demonstrate that Snail1 is expressed in PMCs and plays a pivotal role in maintaining acinar cells within the pancreas in normal and pathological conditions.
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Jordina
authors.initials: J
authors.lastname: Loubat-Casanovas
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Peña
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.|Servei d'Oncologia Mèdica, Hospital del Mar, 08003 Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Gonzàlez
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Alba-Castellón
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.|Escola Superior Infermeria del Mar, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Santi
authors.initials: S
authors.lastname: Rosell
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Francí
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García de Herreros
mesh_terms: D061354:Acinar Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: Snail1; acinar-ductal metaplasia; fibroblast activation; pancreas physiology; pancreatic mesenchymal cells