FCCC LOGO Faculty Publications
Hu ZZ , Kagan BL , Ariazi EA , Rosenthal DS , Zhang LH , Li JV , Huang HZ , Wu C , Jordan VC , Riegel AT , Wellstein A
Proteomic Analysis of Pathways Involved in Estrogen-Induced Growth and Apoptosis of Breast Cancer Cells
PLoS One. 2011 Jun;6(6) :e20410
PMID: ISI:000292092600002    PMCID: PMC3124472    URL: http://www.ncbi.nlm.nih.gov/pubmed/21738574
Back to previous list
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. Methodology/Principal Findings: 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.
Hu, Zhang-Zhi Kagan, Benjamin L. Ariazi, Eric A. Rosenthal, Dean S. Zhang, Lihua Li, Jordan V. Huang, Hongzhan Wu, Cathy Jordan, V. Craig Riegel, Anna T. Wellstein, Anton Department of Defense, Center of Excellence [W81XWH-06-10590]; National Institutes of Health/National Cancer Institute [R01 CA113477, P30 CA051008] This work was supported by the Department of Defense Breast Program W81XWH-06-10590 Center of Excellence Grant (V.C.J., A.W., A.T.R.), National Institutes of Health/National Cancer Institute R01 CA113477 (A.T.R.) and P30 CA051008. Views and opinions of, and endorsements by the author(s) do not reflect those of the U.S. Army or the Department of Defense. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 78 Public library science; 185 berry st, ste 1300, san francisco, ca 94107 usa 783od