Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells
| Autor: | Kasper Thorsen, Bodil Øster, Karin Birkenkamp-Demtröder, Abdelouahid Maghnouj, Claus L. Andersen, Stephan A. Hahn, Francisco Mansilla, Torben F. Ørntoft |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Colorectal cancer proliferation Protein Array Analysis Hyaluronoglucosaminidase colorectal cancer Adenocarcinoma Biology Downregulation and upregulation Cell Movement Cell Adhesion tumour marker medicine Humans Molecular Diagnostics Cell Proliferation Neoplasm Staging Gene knockdown Retinoblastoma Wnt signaling pathway Proteins Methylation Cell cycle medicine.disease Immunohistochemistry Up-Regulation Gene Expression Regulation Neoplastic Wnt Proteins Microscopy Fluorescence Oncology Cancer research cell cycle Colorectal Neoplasms Wnt/β-catenin signalling Signal Transduction |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2011.268 |
| Popis: | Background: The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon β-catenin knockdown. Methods: Transcript profiling was performed on >500 colon biopsies, methylation profiling data were compared with transcript data. Immunohistochemistry assessed KIAA1199 protein expression in 270 stage II/III tumours (>3 years follow-up). The effects of stable KIAA1199 knockdown in SW480 cells (three different constructs) were studied using transcriptional profiling, proliferation and protein analysis. Results: The KIAA1199 transcript was strongly upregulated in 95% of adenocarcinomas. Absent expression in normal mucosa correlated with KIAA1199 promotor methylation. Nuclear and cytoplasmic KIAA1199 protein expression was identified in colon adenocarcinomas and other types of cancers. A subpopulation of patients with tumours strongly expressing KIAA1199 in the nucleus showed a better outcome with regard to recurrence as lung or liver metastases. The KIAA1199 knockdown affected the cell cycle and the Wnt-signalling pathway. Reduced cellular proliferation and decreased KI67, phosphorylated retinoblastoma, β-catenin and ASCL2 protein expression supported these findings. Eighteen Wnt-signalling genes differentially expressed upon KIAA1199 knockdown correlated with the KIAA1199 expression profile in clinical specimens. Conclusion: The KIAA1199 knockdown attenuates the effects of the Wnt/β-catenin signalling and it may thus be regarded as a regulatory part of this pathway. |
| Databáze: | OpenAIRE |
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