NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer

Pancreatic cancer (PC) is characterized by aberrant overexpression of mucins that contribute to its pathogenesis. Although the inflammatory cytokines contribute to mucin overexpression, the mucin profile of PC is markedly distinct from that of normal or inflamed pancreas. We postulated that de novo...

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Veröffentlicht in:	Oncogene 2015-09, Vol.34 (37), p.4879-4889
Hauptverfasser:	Kumar, S, Das, S, Rachagani, S, Kaur, S, Joshi, S, Johansson, S L, Ponnusamy, M P, Jain, M, Batra, S K
Format:	Artikel
Sprache:	eng
Schlagworte:	13 13/106 13/21 13/51 13/89 38 38/61 38/90 631/67/1504/1713 82 82/29 AKT protein Animal models Animals Apoptosis CCL20 protein Cell Biology Cell Transformation, Neoplastic - genetics Cellular proteins Chemokines Chromatin Cytokines Development and progression DNA microarrays Fucose - metabolism Fucosyltransferases - metabolism Gene Expression Profiling Gene Expression Regulation, Neoplastic Genetic aspects Genetic transcription Health aspects Human Genetics Humans Immunohistochemistry Inflammation Internal Medicine Medicine Medicine & Public Health Metastases Metastasis Mice Microarray Analysis Micrococcus Mucin Mucin-1 - genetics Mucin-1 - metabolism Mucin-4 - genetics Mucin-4 - metabolism Mucins NF-κB protein Nuclear Receptor Coactivator 3 - physiology Nuclease Oncology original-article Pancreatic cancer Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Post-translation Properties Protein Processing, Post-Translational - genetics Proteins Retinoic acid Transcription Transcriptional Activation Tumor cell lines Tumor Cells, Cultured Ubiquitin Up-regulation Up-Regulation - genetics
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Zusammenfassung:	Pancreatic cancer (PC) is characterized by aberrant overexpression of mucins that contribute to its pathogenesis. Although the inflammatory cytokines contribute to mucin overexpression, the mucin profile of PC is markedly distinct from that of normal or inflamed pancreas. We postulated that de novo expression of various mucins in PC involves chromatin modifications. Analysis of chromatin modifying enzymes by PCR array identified differential expression of NCOA3 in MUC4-expressing PC cell lines. Immunohistochemistry analysis in tumor tissues from patients and spontaneous mouse models, and microarray analysis following the knockdown of NCOA3 were performed to elucidate its role in mucin regulation and overall impact on PC. Silencing of NCOA3 in PC cell lines resulted in significant downregulation of two most differentially expressed mucins in PC, MUC4 and MUC1 ( P
ISSN:	0950-9232 1476-5594
DOI:	10.1038/onc.2014.409