Journal of Molecular Histology

, Volume 39, Issue 3, pp 283–294

Intestinal adenomagenesis involves core molecular signatures of the epithelial–mesenchymal transition

  • Xiaodi Chen
  • Richard B. Halberg
  • Ryan P. Burch
  • William F. Dove
Original Paper

DOI: 10.1007/s10735-008-9164-3

Cite this article as:
Chen, X., Halberg, R.B., Burch, R.P. et al. J Mol Hist (2008) 39: 283. doi:10.1007/s10735-008-9164-3

Abstract

The epithelial–mesenchymal transition (EMT) occurs commonly during carcinoma invasion and metastasis, but not during early tumorigenesis. Microarray data demonstrated elevation of vimentin, a mesenchymal marker, in intestinal adenomas from ApcMin/+ (Min) mice. We have tested the involvement of EMT in early tumorigenesis in mammalian intestines by following EMT-associated markers. Elevated vimentin RNA expression and protein production were detected within neoplastic cells in murine intestinal adenomas. Similarly, vimentin protein was detected in both adenomas and invasive adenocarcinomas of the human colon, but not in the normal colonic epithelium or in hyperplastic polyps. Expression of E-cadherin varied inversely with vimentin. In addition, the expression of fibronectin was elevated while that of E-cadherin decreased. Canonical E-cadherin suppressors, such as Snail, were not elevated in the same tumor. Elevated vimentin expression in the adenoma was not correlated with persistent Ras signaling, but was strongly correlated with reduced proliferation indices, active Wnt signaling, and TGF-β signaling, as demonstrated by its dependence on Smad3. We designate our observations of expression of only some of the canonical features of EMT as “truncated EMT”. These unexpected observations are interpreted as reflecting the involvement of a core of the EMT system during the tissue remodeling of early tumorigenesis.

Keywords

VimentinApcMinIntestinal adenomaEpithelial–mesenchymal transitionE-cadherin

Abbreviations

1638N

Apc1638N insertion allele

129

129S6

AOM

Azoxymethane

BTBR

BTBR/Pas

B6

C57BL/6J

BR

C57BR/cdcJ

DAB

3,3′-Diaminobenzidine

EMT

Epithelial–mesenchymal transition

IF

Immunofluorescence

IHC

Immunohistochemistry

ISH

In situ hybridization

Min

ApcMin/+

MMP7

Matrix metalloproteinase 7

pMAPK

Phosphorylated-p44/42 mitogen-activated protein kinase

pSmad2

Phosphorylated Smad2

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Xiaodi Chen
    • 1
  • Richard B. Halberg
    • 1
  • Ryan P. Burch
    • 1
  • William F. Dove
    • 1
    • 2
  1. 1.McArdle Laboratory for Cancer ResearchUniversity of WisconsinMadisonUSA
  2. 2.Laboratory of GeneticsUniversity of WisconsinMadisonUSA