NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells
| العنوان: | NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells |
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| المؤلفون: | Ingunn Bakke, Shalini V. Rao, Arne K. Sandvik, Astrid Lægreid, Wenche S. Prestvik, Torunn Bruland, Liv Thommesen, Kristin G. Nørsett, Linn-Karina M. Selvik, Kristine Misund |
| المساهمون: | Norges teknisk-naturvitenskapelige universitet, Det medisinske fakultet, Institutt for kreftforskning og molekylær medisin |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 9, p e76234 (2013) |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Blotting, Western, Active Transport, Cell Nucleus, lcsh:Medicine, Biology, Adenocarcinoma, Real-Time Polymerase Chain Reaction, Stomach Neoplasms, Cell Line, Tumor, Gastrins, Nuclear Receptor Subfamily 4, Group A, Member 2, medicine, Gastric mucosa, Humans, Enterochromaffin-like cell, RNA, Small Interfering, lcsh:Science, Gastrin, Regulation of gene expression, Feedback, Physiological, Multidisciplinary, Gene Expression Profiling, lcsh:R, digestive, oral, and skin physiology, Transfection, medicine.disease, Flow Cytometry, Molecular biology, Immunohistochemistry, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Cell culture, Gene Knockdown Techniques, Cancer research, lcsh:Q, G cell, Butyrate Response Factor 1, hormones, hormone substitutes, and hormone antagonists, Fluorescence Recovery After Photobleaching, Research Article |
| الوصف: | The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells. © 2013 Misund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::452c437ff14d96cf761272bb62d29e7bTest https://pubmed.ncbi.nlm.nih.gov/24086717Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....452c437ff14d96cf761272bb62d29e7b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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