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Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer.

Isinger Ekstrand, Anna LU ; Therkildsen, Christina LU ; Bernstein, Inge and Nilbert, Mef LU (2011) In Familial Cancer 10. p.239-243
Abstract
The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression... (More)
The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by β-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of β-catenin, was present in 54% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Familial Cancer
volume
10
pages
239 - 243
publisher
Kluwer
external identifiers
  • wos:000290937500009
  • pmid:21132538
  • scopus:79958140999
ISSN
1389-9600
DOI
10.1007/s10689-010-9406-x
language
English
LU publication?
yes
id
f7add768-faa0-42a1-8554-94d3c72c4cd7 (old id 1756721)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21132538?dopt=Abstract
date added to LUP
2011-01-03 13:58:45
date last changed
2017-08-27 05:46:03
@article{f7add768-faa0-42a1-8554-94d3c72c4cd7,
  abstract     = {The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by β-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of β-catenin, was present in 54% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer.},
  author       = {Isinger Ekstrand, Anna and Therkildsen, Christina and Bernstein, Inge and Nilbert, Mef},
  issn         = {1389-9600},
  language     = {eng},
  pages        = {239--243},
  publisher    = {Kluwer},
  series       = {Familial Cancer},
  title        = {Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer.},
  url          = {http://dx.doi.org/10.1007/s10689-010-9406-x},
  volume       = {10},
  year         = {2011},
}