title: Proteome-wide profiling of the MCF10AT breast cancer progression model.
abstract: BACKGROUND
  Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer.
  
  
  RESULTS
  We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the "Warburg effect"). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions.
  
  
  CONCLUSIONS
  The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre-neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Lee Yee
authors.initials: LY
authors.lastname: Choong
authors.forename: Simin
authors.initials: S
authors.lastname: Lim
authors.forename: Poh Kuan
authors.initials: PK
authors.lastname: Chong
authors.forename: Chow Yin
authors.initials: CY
authors.lastname: Wong
authors.forename: Nilesh
authors.initials: N
authors.lastname: Shah
authors.forename: Yoon Pin
authors.initials: YP
authors.lastname: Lim
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics*; D020543:Proteome; D053719:Tandem Mass Spectrometry
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome