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ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer
- Source :
- Journal of Translational Medicine, Vol 9, Iss 1, p 211 (2011), Journal of Translational Medicine
- Publication Year :
- 2011
- Publisher :
- BMC, 2011.
-
Abstract
- Background Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients. Methods Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS). Results Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line. Conclusions Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.
- Subjects :
- CA15-3
Fluorescent Antibody Technique
lcsh:Medicine
Apoptosis
Two-dimensional liquid phase chromatographic fractionation
Metastasis
Tissue microarray
Cell Movement
Molecular Targeted Therapy
Aged, 80 and over
Medicine(all)
General Medicine
Hyperplasia
Middle Aged
Mitochondrial Proton-Translocating ATPases
Flow Cytometry
Immunohistochemistry
Gene Expression Regulation, Neoplastic
Female
Antibody
Adult
Breast Neoplasms
Biology
General Biochemistry, Genetics and Molecular Biology
Antibodies
Breast cancer
breast cancer
In vivo
Cell Line, Tumor
ATP synthase α-subunit
medicine
Humans
Neoplasm Invasiveness
Aged
Cell Proliferation
Biochemistry, Genetics and Molecular Biology(all)
Research
Cell Membrane
lcsh:R
Cancer
medicine.disease
Protein Subunits
Tissue Array Analysis
monoclonal antibody
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Immunology
biology.protein
Cancer research
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Translational Medicine
- Accession number :
- edsair.doi.dedup.....6794ae97d0e503f0543419b8101293a3