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ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer

Pan, J and Sun, LC and Tao, YF and Zhou, Z and Du, XL and Peng, L and Feng, X and Wang, J and Li, YP and Liu, L and Wu, SY and Zhang, YL and Hu, SY and Zhao, WL and Zhu, XM and Lou, GL and Ni, J (2011) ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer. Journal of Translational Medicine, 9 (1).

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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. © 2011 Pan et al; licensee BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pan, J
Sun, LC
Tao, YF
Zhou, Zzhz36@pitt.eduZHZ36
Du, XL
Peng, L
Feng, X
Wang, J
Li, YP
Liu, L
Wu, SY
Zhang, YL
Hu, SY
Zhao, WL
Zhu, XM
Lou, GL
Ni, J
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Date: 8 December 2011
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 9
Number: 1
DOI or Unique Handle: 10.1186/1479-5876-9-211
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 01 Nov 2016 17:02
Last Modified: 03 Feb 2019 06:55


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