PMID- 19786015
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20211020
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 316
IP  - 3
DP  - 2010 Feb 1
TI  - SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and 
      maturation of intestinal goblet cells.
PG  - 452-65
LID - 10.1016/j.yexcr.2009.09.020 [doi]
AB  - 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.
CI  - Copyright 2009 Elsevier Inc. All rights reserved.
FAU - Noah, Taeko K
AU  - Noah TK
AD  - Division of Gastroenterology, Cincinnati Children's Hospital Medical Center and 
      University of Cincinnati College of Medicine, Cincinnati, OH, USA.
FAU - Kazanjian, Avedis
AU  - Kazanjian A
FAU - Whitsett, Jeffrey
AU  - Whitsett J
FAU - Shroyer, Noah F
AU  - Shroyer NF
LA  - eng
GR  - DK084167/DK/NIDDK NIH HHS/United States
GR  - DK078392/DK/NIDDK NIH HHS/United States
GR  - DK071686/DK/NIDDK NIH HHS/United States
GR  - R01 CA142826/CA/NCI NIH HHS/United States
GR  - P30 DK078392/DK/NIDDK NIH HHS/United States
GR  - HL090156/HL/NHLBI NIH HHS/United States
GR  - HL095580/HL/NHLBI NIH HHS/United States
GR  - R03 DK084167-01/DK/NIDDK NIH HHS/United States
GR  - R01 HL095580/HL/NHLBI NIH HHS/United States
GR  - K01 DK071686/DK/NIDDK NIH HHS/United States
GR  - R01 HL090156/HL/NHLBI NIH HHS/United States
GR  - R03 DK084167/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090926
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Atoh1 protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Gfi1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (SPDEF protein, human)
RN  - 0 (Spdef protein, mouse)
RN  - 0 (Transcription Factors)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Cell Count
MH  - *Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colonic Neoplasms/genetics/pathology
MH  - DNA-Binding Proteins/metabolism
MH  - Doxycycline/pharmacology
MH  - Epithelial Cells/cytology/drug effects/metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Goblet Cells/*cytology/drug effects/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/drug effects/metabolism/pathology/ultrastructure
MH  - Mice
MH  - Organ Specificity/drug effects
MH  - Protein Transport/drug effects
MH  - Proto-Oncogene Proteins c-ets/genetics/*metabolism
MH  - Stem Cells/cytology/drug effects/metabolism
MH  - Transcription Factors/metabolism
MH  - Transgenes/genetics
PMC - PMC3004755
MID - NIHMS198344
EDAT- 2009/09/30 06:00
MHDA- 2010/02/26 06:00
PMCR- 2011/02/01
CRDT- 2009/09/30 06:00
PHST- 2009/07/06 00:00 [received]
PHST- 2009/09/19 00:00 [revised]
PHST- 2009/09/21 00:00 [accepted]
PHST- 2009/09/30 06:00 [entrez]
PHST- 2009/09/30 06:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - S0014-4827(09)00410-8 [pii]
AID - 10.1016/j.yexcr.2009.09.020 [doi]
PST - ppublish
SO  - Exp Cell Res. 2010 Feb 1;316(3):452-65. doi: 10.1016/j.yexcr.2009.09.020. Epub 
      2009 Sep 26.