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The mitochondrial t...
The mitochondrial transporter SLC25A43 is frequently deleted and may influence cell proliferation in HER2-positive breast tumors
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- Tina, Elisabet, 1975- (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Clinical Research Centre, Örebro University Hospital, Sweden ; School of Health and Medical Sciences, Örebro University, Sweden
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- Lindqvist, Breezy Malakkaran (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,School of Health and Medical Sciences, Örebro University, Sweden
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- Gabrielson, Marike (författare)
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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- Lubovac, Zelmina (författare)
- Högskolan i Skövde,Institutionen för vård och natur,Forskningscentrum för Systembiologi
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- Wegman, Pia (författare)
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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- Wingren, Sten (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,School of Health and Medical Sciences, Örebro University, Sweden
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(creator_code:org_t)
- 2012-08-10
- 2012
- Engelska.
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12:1
- Relaterad länk:
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https://doi.org/10.1...
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https://bmccancer.bi...
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https://his.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Background: Overexpression of the human epidermal growth factor receptor (HER) 2 is associated with poor prognosis and shortened survival in breast cancer patients. HER2 is a potent activator of several signaling pathways that support cell survival, proliferation and metabolism. In HER2-positive breast cancer there are most likely unexplored proteins that act directly or indirectly downstream of well established pathways and take part in tumor development and treatment response.Methods: In order to identify novel copy number variations (CNVs) in HER2-positive breast cancer whole-genome single nucleotide polymorphism (SNP) arrays were used. A PCR-based loss of heterozygosis (LOH) assay was conducted to verify presence of deletion in HER2-positive breast cancer cases but also in HER2 negative breast cancers, cervical cancers and lung cancers. Screening for mutations was performed using single-strand conformation polymorphism (SSCP) followed by PCR sequencing. Protein expression was evaluated with immunohistochemistry (IHC).Results: A common deletion at chromosome Xq24 was found in 80% of the cases. This locus harbors the gene solute carrier (SLC) family 25A member 43 (SLC25A43) encoding for a mitochondrial transport protein. The LOH assay revealed presence of SLC25A43 deletion in HER2-positive (48%), HER2-negative (9%), cervical (42%) and lung (67%) cancers. HER2-positive tumors with negative or low SLC25A43 protein expression had significantly lower S-phase fraction compared to tumors with medium or high expression (P = 0.024).Conclusions: We have found deletion in the SLC25A43 gene to be a common event in HER2-positive breast cancer as well as in other cancers. In addition, the SLC25A43 protein expression was shown to be related to S-phase fraction in HER2-positive breast cancer. Our results indicate a possible role of SLC25A43 in HER2-positive breast cancer and support the hypothesis of altered mitochondrial function in cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Breast cancer
- HER2
- SLC25A43
- S-phase
- Medicin
- Medicine
- Naturvetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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