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Role of reactive oxygen species in calcium signalling in hypoxia-induced epithelial-mesenchymal transition [Poster]
Introduction: Hypoxia is a hallmark of the cancer microenvironment and induces epithelial-mesenchymal transition (EMT) in breast cancer cells. EMT describes the transition of breast cancer cells into a more invasive phenotype. Hypoxia has been reported to cause changes in calcium (Ca2+) signalling in a variety of cell types including osteosarcoma and HEK293 cells, possibly through the production of reactive oxygen species (ROS), however, this pathway has not been studied in breast cancer cells.
Aims: To investigate the role of hypoxia-mediated increases in ROS in the induction of EMT and altered Ca2+ signalling in MDA-MB-468 breast cancer cells.
Methods: MDA-MB-468 breast cancer cells were incubated for 24 h at 1% O2 to induce hypoxia. ROS increases were assessed using a cell-permeable fluorogenic probe 2´,7´-dichlorodihydrofluorescin diacetate (DCFH-DA). Real time RT-PCR was used to assess the mRNA levels of 50 calcium channels and transporters in MDA-MB-468 cells in the presence and absence of hypoxia.
Results: Hypoxia increased levels of the EMT markers vimentin and N-cadherin, and increased intracellular ROS levels. Five Ca2+ permeable channels belonging to different classes were identified as altered by hypoxia in MDAMB- 468 breast cancer cells. Chelation of ROS with 10 mM N-acetylcysteine (NAC) significantly changed the expression pattern of these five selected Ca2+ channels as well as the EMT marker N-cadherin.
Discussion: These results suggest an important role of ROS in hypoxia-mediated EMT in breast cancer cells and indicate that such changes are associated with alterations in the expression of specific Ca2+ permeable ion channels.
History
Publication title
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists Annual Scientific Meeting (ASCEPT2013)Pagination
117Department/School
School of Pharmacy and PharmacologyPublisher
Australasian Society of Clinical and Experimental Pharmacologists and ToxicologistsPlace of publication
AustraliaEvent title
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists Annual Scientific Meeting (ASCEPT2013)Event Venue
Melbourne, AustraliaDate of Event (Start Date)
2013-12-01Date of Event (End Date)
2013-12-04Repository Status
- Restricted