TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumours

0334035 - ÚMG 2010 RIV DE eng J - Journal Article
Oikonomou, E. - Kosmidou, V. - Katseli, A. - Kothonidis, K. - Mourtzoukou, D. - Kontogeorgos, G. - Anděra, Ladislav - Zografos, G. - Pintzas, A.
TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumours.
International Journal of Cancer. Roč. 125, č. 9 (2009), s. 2127-2135. ISSN 0020-7136. E-ISSN 1097-0215
R&D Projects: GA MŠMT 1M0506
Grant - others:EC(XE) LSHC-CT-2006-037278
Institutional research plan: CEZ:AV0Z50520514
Keywords : colorectal tumours * TRAIL receptors expression * KRAS/ BRAF oncogenic mutations
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.722, year: 2009

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.
Permanent Link: http://hdl.handle.net/11104/0178872