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  • Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.

Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.

British journal of cancer (2011-07-21)
K Birkenkamp-Demtroder, A Maghnouj, F Mansilla, K Thorsen, C L Andersen, B Øster, S Hahn, T F Ørntoft
ABSTRACT

The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon β-catenin knockdown. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
GenElute Mammalian Total RNA Miniprep Kit, sufficient for 350 purifications
Sigma-Aldrich
Monoclonal Anti-phospho-Retinoblastoma (pSer795) antibody produced in mouse, ~2 mg/mL, clone RB-10, purified immunoglobulin, buffered aqueous solution