Role of reactive oxygen species in calcium signalling in hypoxia-induced epithelial-mesenchymal transition

Azimi, Iman, Thompson, Erik W, Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2013). Role of reactive oxygen species in calcium signalling in hypoxia-induced epithelial-mesenchymal transition. In: ASCEPT 2013: Abstracts. ASCEPT 2013: Annual Scientific Meeting, Melbourne, VIC, Australia, (117-117). 1-4 December, 2013.

Author Azimi, Iman
Thompson, Erik W
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title of paper Role of reactive oxygen species in calcium signalling in hypoxia-induced epithelial-mesenchymal transition
Conference name ASCEPT 2013: Annual Scientific Meeting
Conference location Melbourne, VIC, Australia
Conference dates 1-4 December, 2013
Proceedings title ASCEPT 2013: Abstracts
Place of Publication Hamilton Central, QLD, Australia
Publisher Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
Publication Year 2013
Sub-type Published abstract
Open Access Status
Start page 117
End page 117
Total pages 1
Language eng
Formatted Abstract/Summary
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.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: School of Pharmacy Publications
 
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Created: Wed, 27 Aug 2014, 11:29:07 EST by Charna Kovacevic on behalf of School of Pharmacy