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Reactive oxygen species and calcium signalling in the induction of hypoxia-mediated epithelial-mesenchymal transition

Citation

Azimi, I and Marcial, DL and Roberts-Thomson, SJ and Monteith, GR, Reactive oxygen species and calcium signalling in the induction of hypoxia-mediated epithelial-mesenchymal transition, ASCEPT-BPS Joint Scientific Meeting: Tomorrow's medicines: pharmacology, patients and populations, 19-21 May 2015, Hong Kong, pp. 23. (2015) [Conference Extract]


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Abstract

Introduction: Hypoxia is a hallmark of the cancer microenvironment and induces epithelial-mesenchymal transition (EMT), a process whereby epithelial cells acquire more migratory and invasive characteristics. Hypoxia can be associated with altered calcium (Ca2+) signalling through the production of reactive oxygen species (ROS), however, this association has not been fully characterised in breast cancer cells.

Aims: To assess the remodelling of Ca2+ signaling and ROS production in a hypoxia model of EMT in MDA-MB-468 breast cancer cells and to define the role of ROS and specific Ca2+ -related proteins in EMT induction in this model.

Methods: To induce EMT, MDA-MB-468 breast cancer cells were incubated in 1% O2. Levels of ROS were assessed using the cell-permeable fluorogenic probe 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA). Quantitative RT-PCR or immunoblotting were used to assess mRNA or protein levels of EMT markers and Ca2+-related proteins. Dharmacon ON-TARGETplus SMARTpool siRNA was used to silence specific Ca2+ channels.

Results: Hypoxia increased the mRNA (24 h) and/or protein levels (48 h) of the EMT markers vimentin, N- cadherin, snail, twist and increased intracellular ROS levels (12 h). Among the fifty Ca2+-related proteins assessed, four underwent significant mRNA up-regulation (3 to 10-fold) with hypoxia. Chelation of ROS with 10 mM N-acetylcysteine (NAC) significantly altered the expression pattern of these Ca2+-related proteins and some EMT markers (N-cadherin). Silencing of TRPC1 channel, one of the four up-regulated Ca2+-related proteins, significantly decreased hypoxia-induced vimentin protein expression.

Discussion: These results implicate an important role for ROS and Ca2+ signalling in the induction of hypoxia-mediated EMT in breast cancer cells.

Item Details

Item Type:Conference Extract
Keywords:reactive oxygen species, calcium signalling, 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)
ID Code:151223
Year Published:2015
Deposited By:Pharmacy
Deposited On:2022-07-25
Last Modified:2022-07-28
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