PMID- 23263765
OWN - NLM
STAT- MEDLINE
DCOM- 20131106
LR  - 20220311
IS  - 1941-6636 (Electronic)
VI  - 44
IP  - 2
DP  - 2013 Jun
TI  - Pro-neoplastic effects of amphiregulin in colorectal carcinogenesis.
PG  - 211-21
LID - 10.1007/s12029-012-9474-2 [doi]
AB  - PURPOSE: Epidermal growth factor (EGF) family plays critical roles in intestinal 
      epithelial growth and transformation. Amphiregulin (AREG) is a member of the EGF 
      family, and has been suggested to be more important to tumor versus normal 
      growth. The precise roles of AREG in colorectal carcinogenesis have not been 
      thoroughly elucidated. METHODS: AREG expression was analyzed in colon cancer 
      specimens using immunohistochemistry. Genetically disruption of AREG in APC 
      (min/+) mouse was achieved by crossbreeding AREG knockout mouse with APC (min/+) 
      mice. Knockdown AREG expression was accomplished by using plasmid-based RNA 
      interference. Growth-stimulatory effects of AREG were determined using cell 
      co-culture systems. RESULTS: AREG was expressed in both epithelial and stromal 
      compartments in human colon cancer; however, it was regulated by different 
      mechanisms. AREG was predominantly regulated at transcriptional level in colon 
      cancer cells while both transcriptional and post-transcriptional mechanisms were 
      involved in colon cancer derived myofibroblasts. Functionally, knockout of AREG 
      strongly reduced tumorigenicity in APC (min/+) mice. Immunohistochemistry 
      demonstrated the coordinate expression of AREG, EGF receptor activity, and cell 
      proliferation marker in APC (min/+) mouse adenoma, indicating the 
      growth-stimulatory function of AREG signaling in tumor development. Furthermore, 
      we demonstrated that AREG may stimulate tumor cell growth through both autocrine 
      and paracrine pathways in cell culture models. Knockdown of AREG impaired the 
      ability of anchorage-independent growth of transformed intestinal epithelial 
      cells. On the other hand, myofibroblast-produced AREG stimulated the growth of 
      colon cancer cells when co-cultured in extracellular matrix. CONCLUSIONS: AREG 
      plays pro-neoplastic roles in colorectal carcinogenesis and may be targeted for 
      colon cancer prevention and treatment.
FAU - Guzman, Michael J
AU  - Guzman MJ
AD  - Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 
      46202, USA.
FAU - Shao, Jinyi
AU  - Shao J
FAU - Sheng, Hongmiao
AU  - Sheng H
LA  - eng
GR  - DK086558/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Gastrointest Cancer
JT  - Journal of gastrointestinal cancer
JID - 101479627
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - Coculture Techniques
MH  - Colorectal Neoplasms/genetics/*metabolism
MH  - EGF Family of Proteins
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Glycoproteins/genetics/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myofibroblasts/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2012/12/25 06:00
MHDA- 2013/11/07 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/11/07 06:00 [medline]
AID - 10.1007/s12029-012-9474-2 [doi]
PST - ppublish
SO  - J Gastrointest Cancer. 2013 Jun;44(2):211-21. doi: 10.1007/s12029-012-9474-2.