Azimi, I and Beilby, H and Davis, FM and Roberts-Thomson, SJ and Monteith, GR, Altered purinergic receptor calcium signalling associated with hypoxia in MDA-MB-468 breast cancer cells [Poster], Proceedings of the Joint ASCEPT-APSA 2012 Conference, 2-5 December 2012, Sydney, Australia, pp. 121. (2012) [Conference Extract]
Official URL: https://www.apsa-online.org/wp-content/uploads/202...
Introduction: Hypoxia is a common feature of the microenvironment of some breast cancers. Hypoxia can induce epithelial-mesenchymal transition (EMT) a process that can convert breast cancer cells into a more invasive phenotype. We have previously shown an association between epidermal growth factor (EGF)-mediated EMT and alterations in purinergic receptor-mediated calcium signalling and levels of puringeric receptor mRNA (e.g. up-regulation of P2X5).
Aims: 1. To compare changes in ATP-induced calcium transients in MDA-MB-468 breast cancer cells in normoxia and hypoxia. 2. To assess mRNA levels of a panel of purinergic receptors in MDA-MB-468 cells in normoxia and hypoxia.
Method: MDA-MB-468 cells were placed in a hypoxic incubator (0.1% O2) for 24 hours at 37°C. Cytosolic free Ca2+ ([Ca2+]CYT) levels were assessed using a Fluorescent Imaging Plate Reader (FLIPR). Changes in mRNA levels were evaluated by quantitative real-time RT-PCR.
Results: Hypoxia-induced EMT was confirmed by changes in EMT markers including vimentin, N-cadherin, snail, and CD24. The nature of the cytosolic calcium response to ATP was altered with hypoxia (e.g. EC50 0.5 μM innormoxia vs 1.3 μM in hypoxia). Significant changes in mRNA levels of some purinergic receptors in response to hypoxia were observed, however, these were often different from those previously observed with EGF-induced EMT.
Discussion: Hypoxia-induced EMT alters ATP-mediated calcium signalling and mRNA levels of purinergic receptors in MDA-MB-468 breast cancer cells. Further studies are required to assess the significance of altered purinegic receptor-mediated Ca2+ signalling associated with the acquisition of EMT.
|Item Type:||Conference Extract|
|Keywords:||purinergic receptor, calcium signalling, hypoxia, breast cancer|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Basic pharmacology|
|Objective Division:||Expanding Knowledge|
|Objective Group:||Expanding knowledge|
|Objective Field:||Expanding knowledge in the health sciences|
|UTAS Author:||Azimi, I (Dr Iman Azimi)|
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