title: Proteomic profiling of Trastuzumab (Herceptin(R))-sensitive and -resistant SKBR-3 breast cancer cells.
abstract: BACKGROUND
  The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear.
  
  
  OBJECTIVE
  To study the effects of short and prolonged trastuzumab treatment on the proteomic profiles of HER-2-overexpressing SKBR-3 BC cells.
  
  
  METHODS
  Cells were treated with trastuzumab to obtain sensitive and resistant clones. The drug effects were evaluated at the phenotypical and proteomic levels.
  
  
  RESULTS
  In the trastuzumab-resistant cells the expression of a large amount of proteins, initially affected by treatment, reverted to levels of the untreated cells.
  
  
  CONCLUSIONS
  The results obtained so far illustrate for the first time a large-scale differential protein expression between trastuzumab-treated and untreated cells, and between trastuzumab-sensitive and resistant cells. We believe that the results obtained will help to increase the knowledge of the molecular effects of trastuzumab and will be useful to better-understand the drug resistance mechanisms.
authors: Centro di Oncobiologia Sperimentale (C.OB.S.), Oncology Department, La Maddalena, Via San Lorenzo Colli 112d, 90146 Palermo, Italy.
authors: Gianluca
authors: G
authors: DI Cara
authors: Germana
authors: G
authors: Marengo
authors: Nadia Ninfa
authors: NN
authors: Albanese
authors: Maria Rita
authors: MR
authors: Marabeti
authors: Rosa
authors: R
authors: Musso
authors: Patrizia
authors: P
authors: Cancemi
authors: Ida
authors: I
authors: Pucci-Minafra
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D059467:Transcriptome / Q000187:drug effects*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab