Lines, KE;
Stevenson, M;
Mihai, R;
Grigorieva, IV;
Shariq, OA;
Gaynor, KU;
Jeyabalan, J;
... Thakker, RV; + view all
(2021)
Hypoxia stimulates angiogenesis and a metabolic switch in human parathyroid adenoma cells.
Endocrine Oncology
, 1
(1)
pp. 23-32.
10.1530/EO-21-0014.
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Abstract
Hypoxia, a primary stimulus for angiogenesis, is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may also be important for parathyroid autotransplantation in patients, are, however, unknown. We, therefore, assessed the effects of hypoxia on gene expression in parathyroid adenoma (PA) cells from patients with primary hyperparathyroidism. Cell suspensions from human PAs were cultured under normoxic or hypoxic conditions and then subjected to cDNA expression analysis. In total, 549 genes were significantly upregulated and 873 significantly downregulated. The most highly upregulated genes (carbonic anhydrase 9 (CA9), Solute carrier family 2A1 (SLC2A1) and hypoxia-inducible lipid droplet-associated protein (HIG2)) had known involvement in hypoxia responses. Dysregulation of oxidative phosphorylation and glycolysis pathway genes were also observed, consistent with data indicating that cells shift metabolic strategy of ATP production in hypoxic conditions and that tumour cells predominantly utilise anaerobic glycolysis for energy production. Proliferation- and angiogenesis-associated genes linked with growth factor signalling, such as mitogen-activated protein kinase kinase 1 (MAP2K1), Jun proto-oncogene (JUN) and ETS proto-oncogene 1 (ETS1), were increased, however, Ras association domain family member 1 (RASSF1), an inhibitor of proliferation was also upregulated, indicating these pathways are unlikely to be biased towards proliferation. Overall, there appeared to be a shift in growth factor signalling pathways from Jak-Stat and Ras signaling to extracellular signal-regulated kinases (ERKs) and hypoxia-inducible factor (HIF)-1α signalling. Thus, our data demonstrate that PAs, under hypoxic conditions, promote the expression of genes known to stimulate angiogenesis, as well as undergoing a metabolic switch.
| Type: | Article |
|---|---|
| Title: | Hypoxia stimulates angiogenesis and a metabolic switch in human parathyroid adenoma cells |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1530/EO-21-0014 |
| Publisher version: | https://doi.org/10.1530/EO-21-0014 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. Published by Bioscientifica Ltd. © 2021 The authors |
| Keywords: | glycolysis, growth factor signalling, hypoxic, metabolic switch |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10177248 |
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