Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: We found production of OPG in colorectal cancer cells to be regulated by beta-catenin/Tcf-4. Addition of exogenous OPG to colorectal cancer cells caused resistance to TRAIL. Similarly, accumulation of OPG in medium of cultivated cells caused resistance to TRAIL, and this could be reverted by removal of OPG. Furthermore, OPG levels were significantly increased in serum of patients with advanced disease. CONCLUSIONS: We conclude that the Wnt/ beta-catenin pathway contributes to carcinogenesis and cancer cell survival by driving expression of OPG. Expression of the survival factor OPG might provide colorectal cancer cells with an essential growth advantage and contribute to cell invasion and metastasis. Inhibition of OPG expression might offer a new therapeutic approach for the treatment of patients with colorectal tumors overexpressing OPG and make these tumors sensitive to TRAIL-induced apoptosis.
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Authors | Enrico N De Toni, Susanne E Thieme, Andreas Herbst, Andrea Behrens, Petra Stieber, Andreas Jung, Helmut Blum, Burkhard Göke, Frank T Kolligs |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 15
Pg. 4713-8
(Aug 01 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18676739
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Osteoprotegerin
- RNA, Small Interfering
- TNF-Related Apoptosis-Inducing Ligand
- beta Catenin
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Topics |
- Apoptosis
- Cell Line, Tumor
- Colonic Neoplasms
(metabolism)
- Colorectal Neoplasms
- Disease Progression
- Drug Resistance, Neoplasm
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Osteoprotegerin
(metabolism)
- RNA, Small Interfering
(metabolism)
- TNF-Related Apoptosis-Inducing Ligand
(metabolism)
- beta Catenin
(metabolism)
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