title: ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer.
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.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Sun
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Tao
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Du
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Shui-Yan
authors.initials: SY
authors.lastname: Wu
authors.forename: Yan-Lan
authors.initials: YL
authors.lastname: Zhang
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Hu
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Zhao
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Zhu
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Lou
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis
chemical_list: D000906:Antibodies; D021122:Protein Subunits; D025261:Mitochondrial Proton-Translocating ATPases