title: Poly(ADP-ribose) polymerase 1 (PARP1) overexpression in human breast cancer stem cells and resistance to olaparib.
abstract: BACKGROUND
  Breast cancer stem cells (BCSCs) have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL), BrCA-MZ-01.
  
  
  METHODS
  ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+) and mature cancer (ALDH-) cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE). Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS.
  
  
  RESULTS
  2-D DIGE identified poly(ADP-ribose) polymerase 1 (PARP1) as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor.
  
  
  CONCLUSIONS
  An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Institut Paoli-Calmettes, Department of Medical Oncology, Marseille, France; Aix-Marseille University, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Gilabert
authors.affiliation: Institut Paoli-Calmettes, Department of Medical Oncology, Marseille, France; Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Launay
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.affiliation: Institut Paoli-Calmettes, Department of Medical Oncology, Marseille, France; Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Aix-Marseille University, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pophillat
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Toiron
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Baudelet
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Institut Paoli-Calmettes, Department of Cancer Genetics, Marseille, France.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Institut Paoli-Calmettes, Department of Cancer Genetics, Marseille, France; Aix-Marseille University, Marseille, France.
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Aix-Marseille University, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.affiliation: Institut Paoli-Calmettes, Department of Biopathology, Marseille, France; Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Aix-Marseille University, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Institut Paoli-Calmettes, Department of Medical Oncology, Marseille, France; Aix-Marseille University, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D010793:Phthalazines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; C531550:olaparib