title: Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation.
abstract: The transcription factor pancreatic and duodenal homeobox factor 1 (PDX-1) is expressed in pancreatic progenitor cells. In exocrine pancreas, PDX-1 is down-regulated during late development, while re-up-regulation of PDX-1 has been reported in pancreatic cancer and pancreatitis. To determine whether sustained expression of PDX-1 could affect pancreas development, PDX-1 was constitutively expressed in all pancreatic lineages by transgenic approaches. The transgenic pancreas was markedly small with the replacement of acinar cells by duct-like structures, accompanied by activated Stat3. Genetic ablation of Stat3 in the transgenic pancreas profoundly suppressed the metaplastic phenotype. These results provide a mechanism of pancreatic metaplasia by which persistent PDX-1 expression cell-autonomously induces acinar-to-ductal transition through Stat3 activation.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiraiwa
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Eric P
authors.initials: EP
authors.lastname: Sandgren
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
mesh_terms: D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics*; D008679:Metaplasia; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein