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

被引：75

作者：

Curry, Merril C. ^{[1
]}

Peters, Amelia A. ^{[1
]}

Kenny, Paraic A. ^{[2
]}

Roberts-Thomson, Sarah J. ^{[1
]}

Monteith, Gregory R. ^{[1
]}

机构：

[1] Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia

[2] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 434卷 / 03期

基金：

英国医学研究理事会;

关键词：

Mitochondrial calcium uniporter; Breast cancer; Calcium; Ionomycin; Cell death; ABT-263; CA2+ TRANSFER; APOPTOSIS; MEMBRANE; SIGNALS; TARGET; LINES;

D O I：

10.1016/j.bbrc.2013.04.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The mitochondrial calcium uniporter (MW) 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. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：695 / 700

页数：6

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