Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells
| Autor: | Merril C. Curry, Sarah J. Roberts-Thomson, Amelia A. Peters, Paraic A. Kenny, Gregory R. Monteith |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Biophysics Antineoplastic Agents Breast Neoplasms Mitochondrion Biology Real-Time Polymerase Chain Reaction Biochemistry chemistry.chemical_compound Cell Line Tumor Internal medicine medicine Humans Gene silencing Gene Silencing RNA Messenger Viability assay skin and connective tissue diseases Receptor Molecular Biology Cell Proliferation Sulfonamides Aniline Compounds Cell growth Ionomycin Cell Biology Mitochondria Endocrinology chemistry Apoptosis Caspases Cancer research Female Calcium Channels |
| Zdroj: | Biochemical and Biophysical Research Communications. 434:695-700 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.04.015 |
| Popis: | The mitochondrial calcium uniporter (MCU) transports free ionic Ca(2+) 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 Ca(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(2+) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect