Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance
作者： Fernando Gallardo , Andreina Padrón , Ricard Garcia-Carbonell , Cristina Rius , Abel González-Perez
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摘要: Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) essential regulator of gene transcription, and its function has been found deregulated different types cancer. In colorectal cancer cells, loss nuclear NCoR induced by Inhibitor kappa B kinase (IKK) through the phosphorylation specific serine residues. We here investigate whether impacts MM, which might have important diagnostic prognostic significance. By IHC, we determined subcellular distribution a cohort 63 primary invasive MM samples, analyzed possible correlation clinical parameters. therefore used microarray-based strategy to determine global expression differences samples similar stage, differ presence cytoplasmic or NCoR. that results upregulation cancer-related genetic signature, significantly associated progression. Inhibition IKK activity cells reverts NCoR-regulated transcription. Analysis public database demonstrated inactivating mutations are highly prevalent showing features driver oncogene.
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