Research article summary (published 30 Oct 2009):

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

Full Abstract

TRAIL raises hopes as a promising anti-tumor agent due to its selectivity toward cancer cells. Higher expression of its pro-death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) attenuates higher sensitivity to TRAIL-induced apoptosis, and represents a marker for better cancer prognosis and treatment. Since receptor availability can be analogous to ligand efficacy, we performed RT-PCR analysis of DR4 and DR5 in 51 colon cancer biopsy specimens and respective normal mucosa, while 11 of these tumors were determined immunohistochemically for protein expression. Transcriptional analysis showed that DR4 and DR5 were significantly upregulated in 37 and 47% of the tumor samples respectively, while both DR4 and DR5 were coinstantaneously upregulated in 31% of the samples analyzed. Positive transcriptional regulation of DRs was recorded as early as Dukes' A stage. Furthermore, protein expression analysis yielded results comparable to DR4 and DR5 increased mRNA levels. Possible contributing events to DR upregulation involve presence of frequent oncogenic mutations in the MAPK pathway, and 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. In the light of recent data concerning TRAIL receptor distribution, we contribute further by presenting DR5 as the most frequently upregulated DR in colon cancer. Furthermore, oncogenic mutations may directly or indirectly enhance DR expression, potentially sensitizing these tumors to TRAIL-based therapies. (c) 2009 UICC.

Author information

Author/s: Oikonomou, Eftychia (E); Kosmidou, Vivian (V); Katseli, Anastasia (A); Kothonidis, Konstantinos (K); Mourtzoukou, Despina (D); Kontogeorgos, George (G); Andera, Ladislav (L); Zografos, Georgios (G); Pintzas, Alexander (A);

Affiliation: Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 9) : pp 2127-35

Dates: Created 2009/09/03; Completed 2009/09/15;

PMID: 19637313, status: MEDLINE (last retrieval date: 9/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Aged Aged, 80 and over Colonic Neoplasms - genetics Female Gene Expression Regulation, Neoplastic Humans Male

Male Middle Aged Mutation Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins B-raf - genetics Receptors, TNF-Related Apoptosis-Inducing Ligand - analysis; genetics; physiology Up-Regulation ras Proteins - genetics

Associated Chemicals: KRAS protein, human (0) ; Proto-Oncogene Proteins (0) ; Receptors, TNF-Related Apoptosis-Inducing Ligand (0) ; BRAF protein, human (EC 2.7.1.37) ; Proto-Oncogene Proteins B-raf (EC 2.7.1.37) ; ras Proteins (EC 3.6.5.2)

Related articles

These are the highest related articles currently in the database:

• High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer. 30 Jul 2008
• Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. 13 Oct 2008
• Mutations in both KRAS and BRAF may contribute to the methylator phenotype in colon cancer. 6 Mar 2008
• CpG island methylation is frequently present in tubulovillous and villous adenomas and correlates with size, site, and villous component. 22 Oct 2007
• Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance. 12 Jun 2008
• Low-grade serous carcinoma of the ovary displaying a macropapillary pattern of invasion. 29 Nov 2008
• Tracing origin of serrated adenomas with BRAF and KRAS mutations. 29 Jun 2005
• Genetic alterations in colorectal cancers with demethylation of insulin-like growth factor II. 9 Jul 2008
• KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer. 16 Nov 2008
• Involvement of the serrated neoplasia pathway in inflammatory bowel disease-related colorectal oncogenesis. 30 Oct 2007

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.