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TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumours
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SYSNO ASEP 0334035 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumours Author(s) Oikonomou, E. (GR)
Kosmidou, V. (GR)
Katseli, A. (GR)
Kothonidis, K. (GR)
Mourtzoukou, D. (GR)
Kontogeorgos, G. (GR)
Anděra, Ladislav (UMG-J) RID
Zografos, G. (GR)
Pintzas, A. (GR)Number of authors 9 Source Title International Journal of Cancer. - : Wiley - ISSN 0020-7136
Roč. 125, č. 9 (2009), s. 2127-2135Number of pages 9 s. Language eng - English Country DE - Germany Keywords colorectal tumours ; TRAIL receptors expression ; KRAS/ BRAF oncogenic mutations Subject RIV EB - Genetics ; Molecular Biology R&D Projects 1M0506 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000270750000016 DOI 10.1002/ijc.24613 Annotation TRAIL raises hopes as a promising anti-tumor agent due to its selectivity toward cancer cells. Since TRAIL receptor availability can be analogous to ligand efficacy, we performed RT-PCR and immunohistochemical analysis of DR4 and DR5 in 51 colon cancer biopsy specimens and respective normal mucosa. The results showed that DR4 and DR5 were significantly upregulated in 37 and 47% of the tumor samples respectively, while both DR4 and DR5 were co-instantaneously upregulated in 31% of the samples analyzed. Positive transcriptional regulation of DRs was recorded as early as Dukes' A stage. Possible contribution of frequent oncogenic mutations in the MAPK pathway was investigated by direct sequencing in all 51 tumors. Samples (6/8) hosting either a KRAS(G12V) or BRAF(V600E) mutation, significantly amplified the upregulated expression of DR4 and DR5, showing strong inter-relation between overexpression and presence of oncogenic KRAS/ BRAF mutations and DRs expression. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2010
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