Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells.
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.
a Department of Radiation Oncology and the Winship Cancer Institute , Emory University , Atlanta , Georgia , USA.|b Department of Anesthesiology , First Hospital of Jilin University , Changchun , China.
Zhiwen
Z
Li
a Department of Radiation Oncology and the Winship Cancer Institute , Emory University , Atlanta , Georgia , USA.
Chi-Ming
CM
Chang
a Department of Radiation Oncology and the Winship Cancer Institute , Emory University , Atlanta , Georgia , USA.
Lanfang
L
Wang
c Department of Hepatobiliary and Pancreatic Surgery , First Hospital of Jilin University , Changchun , China.
Ping
P
Zhang
a Department of Radiation Oncology and the Winship Cancer Institute , Emory University , Atlanta , Georgia , USA.
Hui-Kuo G
HG
Shu
D000596:Amino Acids / Q000008:administration & dosage / Q000172:deficiency*; D045744:Cell Line, Tumor; D003470:Culture Media; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004790:Enzyme Induction; D005910:Glioma / Q000178:diet therapy / Q000201:enzymology*; D006801:Humans; D020935:MAP Kinase Signaling System; D016329:Sp1 Transcription Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000596:Amino Acids; D003470:Culture Media; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
COX-2; Glioblastomas; VEGF; amino acid deprivation; p38-MAPK