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The mitochondrial transport protein SLC25A43 affects drug efficacy and drug-induced cell cycle arrest in breast cancer cell lines
Örebro Univ Hosp, Örebro, Sweden; School of Health & Medical Science, Örebro University, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
2013 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 4, p. 1268-Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 29, no 4, p. 1268-
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-27547DOI: 10.3892/or.2013.2247ISI: 000316510600002PubMedID: 23354756OAI: oai:DiVA.org:oru-27547DiVA, id: diva2:605090
Available from: 2013-02-13 Created: 2013-02-13 Last updated: 2018-08-29Bibliographically approved
In thesis
1. The mitochondrial protein SLC25A43 and it's possible role in HER2-positive breast cancer
Open this publication in new window or tab >>The mitochondrial protein SLC25A43 and it's possible role in HER2-positive breast cancer
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013
Series
Örebro Studies in Medicine, ISSN 1652-4063
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-26797 (URN)
Public defence
2013-01-25, Wilandersalen, Örebro universitetssjukus, Örebro, 13:15 (Swedish)
Opponent
Available from: 2013-01-08 Created: 2013-01-08 Last updated: 2017-10-17Bibliographically approved

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Publisher's full textPubMedhttp://www.spandidos-publications.com/or/29/4/1268

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Tina, Elisabet

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