title: Quantitative proteomics study of breast cancer cell lines isolated from a single patient: discovery of TIMM17A as a marker for breast cancer.
abstract: The proteins involved in breast cancer initiation and progression are still largely elusive. To gain insights into these processes, we conducted quantitative proteomic analyses with 21T series of breast cell lines, which include a normal, primary tumor and a metastatic tumor that were isolated from a single patient. Stable isotope labeling of amino acid in cell culture followed by LC-MS/MS analysis was performed and deregulated proteins were identified using statistical analysis. Gene ontology analysis revealed that proteins involved in metabolic processes were the most deregulated in both tumorigenesis and metastasis. Interaction network analysis indicated that ERBB2 signaling played a critical role in tumorigenesis. In addition to known markers such as ERBB2 and E-cadherin, novel markers, including BRP44L, MTHFD2 and TIMM17A, were found to be overexpressed in 21T breast cancer cells and verified in additional breast cell lines. mRNA expression analysis as well as immunohistochemistry analysis in breast cancer tissues indicated that expression level of TIMM17A was directly correlated with tumor progression, and survival analysis suggested that TIMM17A was a powerful prognosis factor in breast cancer. More interestingly, overexpression and siRNA knockdown experiments indicated an oncogenic activity of TIMM17A in breast cancer. Our study provides a list of potential novel markers for breast cancer tumorigenesis and metastasis using a unique cell model. Further studies on TIMM17A as well as other markers on the list may reveal mechanisms that result in more effective therapeutics for cancer treatment.
authors.affiliation: Cancer Hospital/Cancer Institute, College of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Xiaoen
authors.initials: X
authors.lastname: Xu
authors.forename: Meng
authors.initials: M
authors.lastname: Qiao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Bo
authors.initials: B
authors.lastname: Gu
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Tang
authors.forename: Yihong
authors.initials: Y
authors.lastname: Sun
authors.forename: Wenshu
authors.initials: W
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007553:Isotope Labeling; D053208:Kaplan-Meier Estimate; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D020543:Proteome; C534731:TIMM17A protein, human