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PLoS One. 2014 Aug 21;9(8):e104302. doi: 10.1371/journal.pone.0104302. eCollection 2014.

Poly(ADP-ribose) polymerase 1 (PARP1) overexpression in human breast cancer stem cells and resistance to olaparib.

Author information

1
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.
2
Institut Paoli-Calmettes, Department of Medical Oncology, Marseille, France; Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France.
3
Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
4
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.
5
Institut Paoli-Calmettes, Department of Molecular Pharmacology, Marseille, France; Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France.
6
Institut Paoli-Calmettes, Department of Cancer Genetics, Marseille, France.
7
Institut Paoli-Calmettes, Department of Cancer Genetics, Marseille, France; Aix-Marseille University, Marseille, France.
8
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.
9
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.

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.

CONCLUSION:

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.

PMID:
25144364
PMCID:
PMC4140711
DOI:
10.1371/journal.pone.0104302
[Indexed for MEDLINE]
Free PMC Article

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