title: Proteomic analysis of pathways involved in estrogen-induced growth and apoptosis of breast cancer cells.
abstract: BACKGROUND
  Estrogen is a known growth promoter for estrogen receptor (ER)-positive breast cancer cells. Paradoxically, in breast cancer cells that have been chronically deprived of estrogen stimulation, re-introduction of the hormone can induce apoptosis.
  
  
  RESULTS
  Here, we sought to identify signaling networks that are triggered by estradiol (E2) in isogenic MCF-7 breast cancer cells that undergo apoptosis (MCF-7:5C) versus cells that proliferate upon exposure to E2 (MCF-7). The nuclear receptor co-activator AIB1 (Amplified in Breast Cancer-1) is known to be rate-limiting for E2-induced cell survival responses in MCF-7 cells and was found here to also be required for the induction of apoptosis by E2 in the MCF-7:5C cells. Proteins that interact with AIB1 as well as complexes that contain tyrosine phosphorylated proteins were isolated by immunoprecipitation and identified by mass spectrometry (MS) at baseline and after a brief exposure to E2 for two hours. Bioinformatic network analyses of the identified protein interactions were then used to analyze E2 signaling pathways that trigger apoptosis versus survival. Comparison of MS data with a computationally-predicted AIB1 interaction network showed that 26 proteins identified in this study are within this network, and are involved in signal transduction, transcription, cell cycle regulation and protein degradation.
  
  
  CONCLUSIONS
  G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling pathways were most strongly associated with E2-induced proliferation or apoptosis and are integrated here into a global AIB1 signaling network that controls qualitatively distinct responses to estrogen.
authors: Lombardi Cancer Center, Georgetown University, Washington, DC, United States of America.
authors: Zhang-Zhi
authors: ZZ
authors: Hu
authors: Benjamin L
authors: BL
authors: Kagan
authors: Eric A
authors: EA
authors: Ariazi
authors: Dean S
authors: DS
authors: Rosenthal
authors: Lihua
authors: L
authors: Zhang
authors: Jordan V
authors: JV
authors: Li
authors: Hongzhan
authors: H
authors: Huang
authors: Cathy
authors: C
authors: Wu
authors: V Craig
authors: VC
authors: Jordan
authors: Anna T
authors: AT
authors: Riegel
authors: Anton
authors: A
authors: Wellstein
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D051153:Wnt Proteins; D004958:Estradiol; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; D019869:Phosphatidylinositol 3-Kinases