PMID- 23354756
OWN - NLM
STAT- MEDLINE
DCOM- 20130912
LR  - 20211021
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 29
IP  - 4
DP  - 2013 Apr
TI  - The mitochondrial transport protein SLC25A43 affects drug efficacy and 
      drug-induced cell cycle arrest in breast cancer cell lines.
PG  - 1268-74
LID - 10.3892/or.2013.2247 [doi]
AB  - The mitochondria have been identified as key players of apoptosis, cell 
      proliferation and cell cycle regulation. However, the role of mitochondria in 
      breast cancer and treatment failure remains unclear. We have previously shown a 
      common deletion of the gene SLC25A43 in human epidermal growth factor receptor 2 
      (HER2)-positive breast cancer. This gene is coding for a mitochondrial inner 
      membrane transporter and, to date, little is known about the function of this 
      protein. We have also found that low protein expression of SLC25A43 significantly 
      correlates with a lower S phase fraction in HER2-positive breast cancer. The aim 
      of this study was to investigate whether knockdown (KD) of SLC25A43 could have an 
      effect on the cytotoxicity of different cytostatic drugs using MCF10A, MCF7 and 
      BT-474 cells. Following siRNA-mediated KD of SLC25A43, one non-malignant and two 
      breast cancer cell lines were exposed to the anthracycline epirubicin or the 
      taxane paclitaxel. The HER2-positive breast cancer cells were also exposed to the 
      targeted therapy trastuzumab and dual exposure to trastuzumab and paclitaxel. We 
      found that KD of SLC25A43 resulted in a decreased cytotoxic effect of paclitaxel 
      in the two cancer cell lines (P<0.05). Further analysis of cell cycle phase 
      distribution showed that KD increased the paclitaxel-induced G2/M block in these 
      two cell lines (P<0.05). KD of SLC25A43 also reduced the inhibitory effect of 
      trastuzumab on cell proliferation in the HER2-positive cancer cell line BT-474 
      (P<0.05), and the drug-induced G0/G1 block (P<0.05). Moreover, SLC25A43 
      influenced the percentage of Ki-67-positive cells. Our findings demonstrate that 
      the mitochondrial protein SLC25A43 affects drug efficacy and cell cycle 
      regulation following drug exposure in breast cancer cell lines.
FAU - Gabrielson, Marike
AU  - Gabrielson M
AD  - School of Health and Medical Sciences, Orebro University Hospital, SE-70185 
      Orebro, Sweden. marike.gabrielsson@oru.se
FAU - Tina, Elisabet
AU  - Tina E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130123
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (SLC25A43 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage
MH  - Antineoplastic Agents/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
MH  - Biomarkers, Pharmacological/metabolism
MH  - Breast Neoplasms/*drug therapy/*genetics/pathology
MH  - Cell Cycle Checkpoints/drug effects/genetics
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - MCF-7 Cells
MH  - Mitochondria/genetics/metabolism
MH  - Paclitaxel/*administration & dosage
MH  - Receptor, ErbB-2/genetics
MH  - Trastuzumab
MH  - Tumor Suppressor Proteins/*genetics/metabolism
PMC - PMC3621655
EDAT- 2013/01/29 06:00
MHDA- 2013/09/13 06:00
PMCR- 2013/01/23
CRDT- 2013/01/29 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2012/12/10 00:00 [accepted]
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/09/13 06:00 [medline]
PHST- 2013/01/23 00:00 [pmc-release]
AID - or-29-04-1268 [pii]
AID - 10.3892/or.2013.2247 [doi]
PST - ppublish
SO  - Oncol Rep. 2013 Apr;29(4):1268-74. doi: 10.3892/or.2013.2247. Epub 2013 Jan 23.