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  • Author: R V Thakker x
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K E Lines OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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M Stevenson OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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R Mihai Department of Endocrine Surgery, Oxford University Hospitals NHS Foundation Trust, Headington, Oxford, UK

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I V Grigorieva OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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O A Shariq OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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K U Gaynor OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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J Jeyabalan OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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M Javid OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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R V Thakker OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, UK

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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.

Article Type:
Research Article
DOI:
https://doi.org/10.1530/EO-21-0014
Volume/Issue:
Volume 1: Issue 1
Open access