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

Merril C. Curry, Amelia A. Peters, Paraic A. Kenny, Sarah J. Roberts-Thomson, Gregory R. Monteith

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)695-700
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume434
Issue number3
DOIs
StatePublished - May 10 2013

Keywords

  • ABT-263
  • Breast cancer
  • Calcium
  • Cell death
  • Ionomycin
  • Mitochondrial calcium uniporter

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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