Regulation of TRAIL receptor expression by -catenin in colorectal tumours
| Autor: | W. Boersma-van Ek, de Elisabeth G. E. Vries, Johannes Wesseling, D. M. Heijink, Jan J. Koornstra, Mathilde Jalving, Nynke Zwart, Jan H. Kleibeuker, de Steven Jong, Willem Sluiter |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON) |
| Rok vydání: | 2013 |
| Předmět: |
Adenoma
Adult Male Cancer Research medicine.medical_specialty Beta-catenin Adolescent Receptor expression Down-Regulation Colorectal adenoma Biology Cell Line TNF-Related Apoptosis-Inducing Ligand Young Adult Downregulation and upregulation Cell Line Tumor Internal medicine Receptors 80 and over medicine Humans Child Receptor beta Catenin Aged Neoplasm Staging Aged 80 and over Regulation of gene expression Neoplastic Tumor Carcinoma General Medicine Middle Aged medicine.disease Tumor Burden Gene Expression Regulation Neoplastic Protein Transport Receptors TNF-Related Apoptosis-Inducing Ligand Endocrinology Gene Expression Regulation Apoptosis Catenin Cancer research biology.protein Female Neoplasm Grading Colorectal Neoplasms Protein Binding |
| Zdroj: | CARCINOGENESIS, 35(5), 1092-1099. Oxford University Press |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgt484 |
| Popis: | Expression of the pro-apoptotic TRAIL receptors is regulated, at least in part, by beta-catenin. We show that beta-catenin co-localizes with DR4/5 in human and mouse colorectal tumours and that downregulation of beta-catenin in cell line models reduces TRAIL receptor expression and TRAIL sensitivity.Tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) is being investigated as a targeted cancer therapeutic and the expression of its pro-apoptotic receptors, DR4 and DR5, increases during colorectal carcinogenesis. This study investigated the role of beta-catenin in the regulation of these receptors. In human colorectal adenoma and carcinoma cell lines, downregulation of beta-catenin resulted in lower total DR4 and DR5 protein levels. Similarly, cell membrane expression of DR4 and DR5 was reduced after downregulation of beta-catenin in colon carcinoma cells, whereas induction of beta-catenin in HeLa cells led to increased cell membrane expression of DR4 and DR5. Downregulation of beta-catenin decreased the recombinant human TRAIL sensitivity of human colon carcinoma cells. Activation of the transcription factor T-cell factor-4 (TCF-4) is an important function of beta-catenin. Dominant-negative TCF-4 overexpression, however, did not significantly affect TRAIL receptor expression or recombinant human TRAIL sensitivity. Human colorectal adenomas (N = 158) with aberrant (cytoplasmic and nuclear) beta-catenin expression had a higher percentage of immunohistochemical DR4 and DR5 staining per tumour (mean: 73 and 88%, respectively) than those with membranous beta-catenin staining only (mean: 50 and 70%, respectively, P |
| Databáze: | OpenAIRE |
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