Document Detail


The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis.
MedLine Citation:
PMID:  23355395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example, acinar-ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal development, ADM, and the progression of normal cells to PanIN lesions, we undertook a systematic approach to identify the Prrx1 paired homeodomain Prrx1 transcriptional factor as a highly regulated gene in these processes. Prrx1 annotates a subset of pancreatic ductal epithelial cells in Prrx1creER(T2)-IRES-GFP mice. Furthermore, sorted Prrx1(+) cells have the capacity to self-renew and expand during chronic pancreatitis. The two isoforms, Prrx1a and Prrx1b, regulate migration and invasion, respectively, in pancreatic cancer cells. In addition, Prrx1b is enriched in circulating pancreatic cells (Pdx1cre;LSL-Kras(G12D/+);p53(fl/+);R26YFP). Intriguingly, the Prrx1b isoform, which is also induced in ADM, binds the Sox9 promoter and positively regulates Sox9 expression. This suggests a new hierarchical scheme whereby a Prrx1-Sox9 axis may influence the emergence of acinar-ductal metaplasia and regeneration. Furthermore, our data provide a possible explanation of why pancreatic cancer is skewed toward a ductal fate.
Authors:
Maximilian Reichert; Shigetsugu Takano; Johannes von Burstin; Sang-Bae Kim; Ju-Seog Lee; Kaori Ihida-Stansbury; Christopher Hahn; Steffen Heeg; Günter Schneider; Andrew D Rhim; Ben Z Stanger; Anil K Rustgi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-25
Journal Detail:
Title:  Genes & development     Volume:  27     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-03-22     Revised Date:  2014-01-15    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-300     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cells, Cultured
Gene Expression Profiling
Gene Expression Regulation
Homeodomain Proteins / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Pancreas / cytology,  pathology*,  physiology*
Pancreatic Neoplasms / physiopathology*
Promoter Regions, Genetic / genetics
Protein Binding
Protein Isoforms / metabolism
Regeneration / physiology*
SOX9 Transcription Factor / genetics
Grant Support
ID/Acronym/Agency:
CA117969/CA/NCI NIH HHS; DK007066/DK/NIDDK NIH HHS; DK060694/DK/NIDDK NIH HHS; DK083111/DK/NIDDK NIH HHS; DK083355/DK/NIDDK NIH HHS; DK088945/DK/NIDDK NIH HHS; K08 DK088945/DK/NIDDK NIH HHS; P30 CA016520/CA/NCI NIH HHS; P30-DK050306/DK/NIDDK NIH HHS; R01 DK060694/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Protein Isoforms; 0/Prrx1 protein, mouse; 0/SOX9 Transcription Factor; 0/Sox9 protein, mouse
Comments/Corrections

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