title: Radiation-induced Notch signaling in breast cancer stem cells.
abstract: OBJECTIVE
  To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation.
  
  
  METHODS
  Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription-polymerase chain reaction to study the Notch pathway in response to radiation.
  
  
  RESULTS
  We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose-dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool.
  
  
  CONCLUSIONS
  Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.
authors.affiliation: Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
authors.forename: Chann
authors.initials: C
authors.lastname: Lagadec
authors.forename: Erina
authors.initials: E
authors.lastname: Vlashi
authors.forename: Yazeed
authors.initials: Y
authors.lastname: Alhiyari
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Phillips
authors.forename: Milana
authors.initials: M
authors.lastname: Bochkur Dratver
authors.forename: Frank
authors.initials: F
authors.lastname: Pajonk
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects*; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000528:radiation effects; D018874:Spheroids, Cellular / Q000378:metabolism / Q000528:radiation effects
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; C511877:Dll3 protein, mouse; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D053829:Amyloid Precursor Protein Secretases