Abstract
BackgroundTreatment 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.MethodsDifferential 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).ResultsUp 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.ConclusionsOver-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.
Highlights
Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs
The display map of differentially expressed proteins between the MCF-7-H and MCF-7 cell lines and the MALDI-TOF/MS tryptic peptide mass map of ATP synthase a-subunit are shown in Figure 1B and 1C, respectively
Since ATP synthase a-subunit was highly over-expressed in 94.6% of breast cancer samples tested while being undetectable in normal breast tissues, this study was focused on the expression, functional implication and potential involvement of ATP synthase in the progression and metastasis of breast cancer
Summary
Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients. Studies of molecular alterations in tumors have successfully elucidated some mechanisms of mammary and others do not adequately identify patients at an early stage, increasing the risk of progression and metastasis [6]. Among the currently available techniques, proteomic analysis by two-dimensional mass spectrometry (2DE-MS) permits the screening of thousands of modified or unmodified proteins simultaneously, becoming increasingly popular for identifying biomarkers for early detection, classification and prognosis of tumors, as well as pinpointing targets for improved treatment outcomes [8,10]. The precise detection of isoforms and/ or proteins with post-translational modifications that alter the pI and/or hydrophobicity is enhanced
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