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Imbalanced expression of Tif1γ inhibits pancreatic ductal epithelial cell growth.
MedLine Citation:
PMID:  24959375     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Transcriptional intermediary factor 1 gamma (Tif1γ) (Ectodermin/PTC7/RFG7/TRIM33) is a transcriptional cofactor with an important role in the regulation of the TGFβ pathway. It has been suggested that it competes with Smad2/Smad3 for binding to Smad4, or alternatively that it may target Smad4 for degradation, although its role in carcinogenesis is unclear. In this study, we showed that Tif1γ interacts with Smad1/Smad4 complex in vivo, using both yeast two-hybrid and coimmunoprecipitation assays. We demonstrated that Tif1γ inhibits transcriptional activity of the Smad1/Smad4 complex through its PHD domain or bromo-domainin pancreatic cells by luciferase assay. Additionally, there is a dynamic inverse relationship between the levels of Tif1γ and Smad4 in benign and malignant pancreatic cell lines. Overexpression of Tif1γ resulted in decreased level of Smad4. Both overexpression and knockdown of Tif1γ resulted in growth inhibition in both benign and cancerous pancreatic cell lines, attributable to a G2-phase cell cycle arrest, but only knockdown of Tif1γ reduces tumor cell invasiveness in vitro. Our study demonstrated that imbalanced expression of Tif1γ results in inhibition of pancreatic ductal epithelial cell growth. In addition, knockdown of Tif1γ may inhibit tumor invasion. These data suggest that Tif1γ might serve as a potential therapeutic target for pancreatic cancer.
Authors:
Martin Ligr; Xinyu Wu; Garrett Daniels; David Zhang; Huamin Wang; Cristina Hajdu; Jinhua Wang; Ruimin Pan; Zhiheng Pei; Lanjing Zhang; Marcovalerio Melis; Matthew R Pincus; John K Saunders; Peng Lee; Ruliang Xu
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Publication Detail:
Type:  Journal Article     Date:  2014-05-26
Journal Detail:
Title:  American journal of cancer research     Volume:  4     ISSN:  2156-6976     ISO Abbreviation:  Am J Cancer Res     Publication Date:  2014  
Date Detail:
Created Date:  2014-06-24     Completed Date:  2014-06-24     Revised Date:  2014-06-26    
Medline Journal Info:
Nlm Unique ID:  101549944     Medline TA:  Am J Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  196-210     Citation Subset:  -    
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