title: Identification of novel kinase targets for the treatment of estrogen receptor-negative breast cancer.
abstract: OBJECTIVE
  Previous gene expression profiling studies of breast cancer have focused on the entire genome to identify genes differentially expressed between estrogen receptor (ER) alpha-positive and ER-alpha-negative cancers.
  
  
  METHODS
  Here, we used gene expression microarray profiling to identify a distinct kinase gene expression profile that identifies ER-negative breast tumors and subsets ER-negative breast tumors into four distinct subtypes.
  
  
  RESULTS
  Based on the types of kinases expressed in these clusters, we identify a cell cycle regulatory subset, a S6 kinase pathway cluster, an immunomodulatory kinase-expressing cluster, and a mitogen-activated protein kinase pathway cluster. Furthermore, we show that this specific kinase profile is validated using independent sets of human tumors and is also seen in a panel of breast cancer cell lines. Kinase expression knockdown studies show that many of these kinases are essential for the growth of ER-negative, but not ER-positive, breast cancer cell lines. Finally, survival analysis of patients with breast cancer shows that the S6 kinase pathway signature subtype of ER-negative cancers confers an extremely poor prognosis, whereas patients whose tumors express high levels of immunomodulatory kinases have a significantly better prognosis.
  
  
  CONCLUSIONS
  This study identifies a list of kinases that are prognostic and may serve as druggable targets for the treatment of ER-negative breast cancer.
authors.affiliation: Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Speers
authors.forename: Anna
authors.initials: A
authors.lastname: Tsimelzon
authors.forename: Krystal
authors.initials: K
authors.lastname: Sexton
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Herrick
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez
authors.forename: Aedin
authors.initials: A
authors.lastname: Culhane
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Susan
authors.initials: S
authors.lastname: Hilsenbeck
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang
authors.forename: Powel
authors.initials: P
authors.lastname: Brown
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009376:Neoplasms, Hormone-Dependent; D011960:Receptors, Estrogen / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011960:Receptors, Estrogen; D019893:Ribosomal Protein S6 Kinases