PMID- 18220315
OWN - NLM
STAT- MEDLINE
DCOM- 20080508
LR  - 20211020
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 214
IP  - 5
DP  - 2008 Apr
TI  - Lack of interleukin-4 receptor alpha chain-dependent signalling promotes 
      azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice.
PG  - 603-9
LID - 10.1002/path.2316 [doi]
AB  - Interleukin (IL)-4 receptor (IL-4R) alpha chain-dependent signalling by IL-4 and 
      IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. 
      However, the role of IL-4R alpha-dependent signalling during the early, 
      pre-malignant stages of colorectal carcinogenesis has not been investigated. 
      Therefore, we investigated the effect of deletion of the IL-4R alpha gene on 
      azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size 
      in Balb/c mice. IL-4R alpha(-/-) mice developed significantly more ACFs [median 
      8, inter-quartile range (IQR) 4-11.5; n = 9] than wild-type (WT) animals (median 
      4, IQR 1-6; n = 9; p = 0.04, Mann-Whitney U-test). There were significantly 
      higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4R 
      alpha(-/-) mice than WT animals, but no difference in serum IL-13 levels. In the 
      absence of functional IL-4Rs, IL-13 can also signal via the IL-13R alpha2 
      receptor, leading to induction of transforming growth factor (TGF) beta, which 
      has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We 
      found that mucosal TGFbeta mRNA levels and intestinal epithelial cell TGFbeta 
      immunoreactivity were significantly higher in IL-4R alpha(-/-) mice than in WT 
      animals. In summary, IL-4R alpha-dependent signalling has a protective, 
      anti-neoplastic role during the post-initiation phase of azoxymethane-induced 
      colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough 
      investigation of the role of IL-4R alpha-dependent signalling during human 
      colorectal carcinogenesis, particularly as antagonism of IL-4R signalling 
      represents a therapeutic strategy for asthma and other allergic diseases.
CI  - Copyright (c) 2008 Pathological Society of Great Britain and Ireland
FAU - Ko, C W S
AU  - Ko CW
AD  - Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, 
      University of Leeds, Wellcome Trust Brenner Building, St James's University 
      Hospital, Leeds LS9 7TF, UK. mrpcwsk@leeds.ac.uk
FAU - Cuthbert, R J
AU  - Cuthbert RJ
FAU - Orsi, N M
AU  - Orsi NM
FAU - Brooke, D A
AU  - Brooke DA
FAU - Perry, S L
AU  - Perry SL
FAU - Markham, A F
AU  - Markham AF
FAU - Coletta, P L
AU  - Coletta PL
FAU - Hull, M A
AU  - Hull MA
LA  - eng
GR  - G116/146/MRC_/Medical Research Council/United Kingdom
GR  - CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Carcinogens)
RN  - 0 (Il4ra protein, mouse)
RN  - 0 (Interleukin-13)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
RN  - MO0N1J0SEN (Azoxymethane)
SB  - IM
MH  - Animals
MH  - Azoxymethane
MH  - Carcinogens
MH  - Cell Transformation, Neoplastic/immunology/pathology
MH  - Colorectal Neoplasms/chemically induced/*immunology/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Interleukin-13/blood
MH  - Interleukin-4/blood
MH  - Intestinal Mucosa/immunology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Precancerous Conditions/chemically induced/*immunology/pathology
MH  - Receptors, Cell Surface/deficiency/*immunology
MH  - Signal Transduction/immunology
MH  - Transforming Growth Factor beta1/metabolism
MH  - Tumor Necrosis Factor-alpha/blood
EDAT- 2008/01/29 09:00
MHDA- 2008/05/09 09:00
CRDT- 2008/01/29 09:00
PHST- 2008/01/29 09:00 [pubmed]
PHST- 2008/05/09 09:00 [medline]
PHST- 2008/01/29 09:00 [entrez]
AID - 10.1002/path.2316 [doi]
PST - ppublish
SO  - J Pathol. 2008 Apr;214(5):603-9. doi: 10.1002/path.2316.