Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells

• Type of Material: Article
• Authors: Zhiwen Li, Emory University School of Medicine; Chi-Ming Chang, Emory University School of Medicine; Lanfang Wang, Emory University School of Medicine; Ping Zhang, Jilin University; Hui-Kuo Shu, Emory University
• Language: English
• Date: 2017-04-21
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Taylor & Francis Group, LLC.
• Final Published Version (URL): http://dx.doi.org/10.1080/07357907.2017.1292517
• Title of Journal or Parent Work: Cancer Investigation
• ISSN: 0735-7907
• Volume: 35
• Issue: 4
• Start Page: 237
• End Page: 247
• Grant/Funding Information: A Cancer Center grant (to Emory University) from the National Cancer Institute (P30-CA138292) also provided partial support for this work.; Work supported in part by grant (to H.G.S.) from the Southeast Brain Tumor Foundation and fellowship (to Z.L.) from the National Clinical Key Specialist Foundation to Anesthesiology Department of First Hospital of Jilin University.
• Keywords: Humans; Culture Media; Amino Acids; Cell Line, Tumor; COX-2; Glioma; Vascular Endothelial Growth Factor A; p38 Mitogen-Activated Protein Kinases; Cyclooxygenase 2; amino acid deprivation; MAP Kinase Signaling System; p38-MAPK; Enzyme Induction; Sp1 Transcription Factor; VEGF; Glioblastomas
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Chemistry, Radiation

Abstract

Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Increased vascular endothelial growth factor expression results from starvation-dependent COX-2 induction. These data suggest that COX-2 induction with amino acid deprivation may be a part of the adaptation of glioma cells to these conditions, and potentially alter cellular response to anti-neoplastic therapy.