English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A colorectal cancer expression profile that includes transforming growth factor ß inhibitor BAMBI predicts metastatic potential

Fritzmann, J., Morkel, M., Besser, D., Budczies, J., Frauke, K., Brembeck, F. H., et al. (n.d.). A colorectal cancer expression profile that includes transforming growth factor ß inhibitor BAMBI predicts metastatic potential. Gastroenterology, 137(1), 165-175. doi:10.1053/j.gastro.2009.03.041.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8CF3-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8CF5-3
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Fritzmann, Johannes, Author
Morkel, Markus1, Author              
Besser, Daniel, Author
Budczies, Jan, Author
Frauke, Kosel, Author
Brembeck, Felix H., Author
Stein, Ulrike, Author
Fichtner, Iduna, Author
Schlag, Peter M., Author
Birchmeier, Walter, Author
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

Content

show
hide
Free keywords: -
 Abstract: Background & Aims Much is known about the genes and mutations that cause colorectal cancer (CRC), yet only a few have been associated with CRC metastasis. We performed expression-profiling experiments to identify genetic markers of risk and to elucidate the molecular mechanisms of CRC metastasis. Methods We compared gene expression patterns between metastatic and nonmetastatic stage-matched human colorectal carcinomas by microarray analysis. Correlations between BAMBI and metastasis-free survival were examined by quantitative real-time polymerase chain reaction (PCR) using an independent set of human colon carcinomas. Human colon cancer cell lines were analyzed for BAMBI regulation, cell motility, and experimental metastasis. Results We established a signature of 115 genes that differentiated metastatic from nonmetastatic primary tumors. Among these, the transforming growth factor (TGF) β inhibitor BAMBI was highly expressed in approximately half of metastatic primary tumors and metastases but not in nonmetastatic tumors. BAMBI is a target of canonical Wnt signaling that involves the β-catenin coactivator BCL9-2. We observed an inverse correlation between level of BAMBI expression and metastasis-free survival time of patients. BAMBI inhibits TGF-β signaling and increases migration in colon cancer cells. In mice, overexpression of BAMBI caused colon cancer cells to form tumors that metastasized more frequently to liver and lymph nodes than control cancer cells. Conclusions BAMBI regulates CRC metastasis by connecting the Wnt/β-catenin and TGF-β-signaling pathways. The metastatic expression signature we describe, along with BAMBI levels, can be used in prognosis. Developmental signaling pathways appear to act in hierarchies and cooperate in tumor cell migration, invasion, and metastasis.

Details

show
hide
Language(s): eng - English
 Dates:
 Publication Status: Not specified
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 460808
DOI: 10.1053/j.gastro.2009.03.041
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Gastroenterology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 137 (1) Sequence Number: - Start / End Page: 165 - 175 Identifier: ISSN: 0016-5085