Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

Curry, Merril C., Peters, Amelia A., Kenny, Paraic A., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2013) Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells. Biochemical and Biophysical Research Communications, 434 3: 695-700. doi:10.1016/j.bbrc.2013.04.015

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Author Curry, Merril C.
Peters, Amelia A.
Kenny, Paraic A.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
1090-2104
Publication date 2013-05-10
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2013.04.015
Open Access Status File (Author Post-print)
Volume 434
Issue 3
Start page 695
End page 700
Total pages 6
Place of publication Philadelphia, PA, United States
Publisher Academic Press
Collection year 2014
Language eng
Formatted abstract
The mitochondrial calcium uniporter (MCU) transports free ionic Ca2+ into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca2+ levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca2+ levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.
Keyword Mitochondrial calcium uniporter
Breast cancer
Calcium
Ionomycin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
 
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