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

• Published in: Genes & development Vol. 20; no. 11; pp. 1435 - 1440
• Main Authors: Miyatsuka, Takeshi, 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
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2006
• Subjects: Animals; Homeodomain Proteins - genetics; Metaplasia; Mice; Mice, Knockout; Mice, Transgenic; Pancreas - metabolism; Pancreas - pathology; Research Communication; STAT3 Transcription Factor - metabolism; Trans-Activators - genetics
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1412806

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.