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PMID: 16751181 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation.

Genes & development ·Vol. 20 ·No. 11 ·2006-06-01 ·Pages 1435-40

Miyatsuka T, Kaneto H, Shiraiwa T, Matsuoka TA, Yamamoto K, Kato K, Nakamura Y, Akira S, Takeda K, Kajimoto Y, Yamasaki Y, Sandgren EP, Kawaguchi Y, Wright CV, Fujitani Y

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.

MeSH Terms
Animals Homeodomain Proteins/genetics Metaplasia Mice Mice, Knockout Mice, Transgenic Pancreas/metabolism,pathology STAT3 Transcription Factor/metabolism Trans-Activators/genetics
Chemicals
Homeodomain Proteins STAT3 Transcription Factor Trans-Activators pancreatic and duodenal homeobox 1 protein
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Miyatsuka Takeshi
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Kaneto Hideaki
Shiraiwa Toshihiko
Matsuoka Taka-aki
Yamamoto Kaoru
Kato Ken
Nakamura Yumiko
Akira Shizuo
Takeda Kiyoshi
Kajimoto Yoshitaka
Yamasaki Yoshimitsu
Sandgren Eric P
Kawaguchi Yoshiya
Wright Christopher V E
Fujitani Yoshio
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1412806
Published
2006-06-01
Pages
1435-40
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1475756
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1412806 PMC Full Text View journal details
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