PMID- 24833705
OWN - NLM
STAT- MEDLINE
DCOM- 20140829
LR  - 20220311
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 307
IP  - 1
DP  - 2014 Jul 1
TI  - Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in 
      multiple distal colonic tumors with features of familial adenomatous polyposis.
PG  - G16-23
LID - 10.1152/ajpgi.00358.2013 [doi]
AB  - Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation 
      in adenomatous polyposis coli (APC). The major clinical manifestation is 
      development of multiple colonic tumors at a young age due to stochastic loss of 
      the remaining APC allele. Extracolonic features, including periampullary tumors, 
      gastric abnormalities, and congenital hypertrophy of the retinal pigment 
      epithelium, may occur. The objective of this study was to develop a mouse model 
      that simulates these features of FAP. We combined our Lrig1-CreERT2/+ mice with 
      Apcfl/+ mice, eliminated one copy of Apc in leucine-rich repeats and 
      immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1(+)) progenitor 
      cells with tamoxifen injection, and monitored tumor formation in the colon by 
      colonoscopy and PET. Initial loss of one Apc allele in Lrig1(+) cells results in 
      a predictable pattern of preneoplastic changes, culminating in multiple distal 
      colonic tumors within 50 days of induction, as well as the extracolonic 
      manifestations of FAP mentioned above. We show that tumor formation can be 
      monitored by noninvasive PET imaging. This inducible stem cell-driven model 
      recapitulates features of FAP and offers a tractable platform on which 
      therapeutic interventions can be monitored over time by colonoscopy and 
      noninvasive imaging.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Powell, Anne E
AU  - Powell AE
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, 
      Tennessee;
FAU - Vlacich, Gregory
AU  - Vlacich G
AD  - Department of Radiation Oncology, Vanderbilt University Medical Center, 
      Nashville, Tennessee;
FAU - Zhao, Zhen-Yang
AU  - Zhao ZY
AD  - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, 
      Tennessee;
FAU - McKinley, Eliot T
AU  - McKinley ET
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, 
      Tennessee;
FAU - Washington, M Kay
AU  - Washington MK
AD  - Department of Pathology, Vanderbilt University Medical Center, Nashville, 
      Tennessee;
FAU - Manning, H Charles
AU  - Manning HC
AD  - Vanderbilt Institute for Imaging Science, Vanderbilt University Medical Center, 
      Nashville, Tennessee; and.
FAU - Coffey, Robert J
AU  - Coffey RJ
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, 
      Tennessee; Department of Cell and Developmental Biology, Vanderbilt University 
      Medical Center, Nashville, Tennessee robert.coffey@vanderbilt.edu.
LA  - eng
GR  - R01 CA-163806/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA-151566/CA/NCI NIH HHS/United States
GR  - T32 CA119925/CA/NCI NIH HHS/United States
GR  - R01 CA-140628/CA/NCI NIH HHS/United States
GR  - R01 CA151566/CA/NCI NIH HHS/United States
GR  - R25 CA092043/CA/NCI NIH HHS/United States
GR  - U01 CA-084239/CA/NCI NIH HHS/United States
GR  - K25 CA-12739/CA/NCI NIH HHS/United States
GR  - T32 CA-119925/CA/NCI NIH HHS/United States
GR  - R01 CA163806/CA/NCI NIH HHS/United States
GR  - P50 CA-095103/CA/NCI NIH HHS/United States
GR  - R01 CA-46413/CA/NCI NIH HHS/United States
GR  - R25 CA-136440/CA/NCI NIH HHS/United States
GR  - R01 CA046413/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140515
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Lrig1 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Adenomatous Polyposis Coli/diagnostic imaging/genetics/*metabolism/pathology
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/metabolism/pathology
MH  - Colon/diagnostic imaging/*metabolism/pathology
MH  - Colonoscopy
MH  - Disease Models, Animal
MH  - *Genes, APC
MH  - Hypertrophy
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Positron-Emission Tomography
MH  - Precancerous Conditions/diagnostic imaging/genetics/*metabolism/pathology
MH  - Retinal Pigment Epithelium/metabolism/pathology
MH  - Time Factors
PMC - PMC4080164
OTO - NOTNLM
OT  - colorectal cancer
OT  - mouse models
OT  - stem cells
EDAT- 2014/05/17 06:00
MHDA- 2014/08/30 06:00
PMCR- 2015/07/01
CRDT- 2014/05/17 06:00
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2014/08/30 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - ajpgi.00358.2013 [pii]
AID - GI-00358-2013 [pii]
AID - 10.1152/ajpgi.00358.2013 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2014 Jul 1;307(1):G16-23. doi: 
      10.1152/ajpgi.00358.2013. Epub 2014 May 15.