Document Detail


SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells.
MedLine Citation:
PMID:  19786015     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation.
METHODS: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined.
RESULTS: In LS174T colon cancer cells treated with Notch/gamma-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation.
CONCLUSIONS: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.
Authors:
Taeko K Noah; Avedis Kazanjian; Jeffrey Whitsett; Noah F Shroyer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-26
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-25     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  452-65     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Transcription Factors / metabolism
Cell Count
Cell Differentiation* / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Colonic Neoplasms / genetics,  pathology
DNA-Binding Proteins / metabolism
Doxycycline / pharmacology
Epithelial Cells / cytology,  drug effects,  metabolism
Gene Expression Regulation, Neoplastic / drug effects
Goblet Cells / cytology*,  drug effects,  metabolism*
Humans
Intestinal Mucosa / drug effects,  metabolism,  pathology,  ultrastructure
Mice
Organ Specificity / drug effects
Protein Transport / drug effects
Proto-Oncogene Proteins c-ets / genetics,  metabolism*
Stem Cells / cytology,  drug effects,  metabolism
Transcription Factors / metabolism
Transgenes / genetics
Grant Support
ID/Acronym/Agency:
DK071686/DK/NIDDK NIH HHS; DK078392/DK/NIDDK NIH HHS; DK084167/DK/NIDDK NIH HHS; HL090156/HL/NHLBI NIH HHS; HL095580/HL/NHLBI NIH HHS; R01 CA142826/CA/NCI NIH HHS; R01 HL095580/HL/NHLBI NIH HHS; R03 DK084167/DK/NIDDK NIH HHS; R03 DK084167-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Atoh1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA-Binding Proteins; 0/Gfi1 protein, mouse; 0/Proto-Oncogene Proteins c-ets; 0/SPDEF protein, human; 0/Spdef protein, mouse; 0/Transcription Factors; N12000U13O/Doxycycline
Comments/Corrections

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