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BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma
The Journal of pathology, 2012-06, Vol.227 (2), p.200-208
Busacca, Sara
Sheaff, Michael
Arthur, Kenneth
Gray, Steven G
O'Byrne, Kenneth J
Richard, Derek J
Soltermann, Alex
Opitz, Isabelle
Pass, Harvey
Harkin, D Paul
Quinn, Jennifer E
Fennell, Dean A
2012
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Busacca, Sara
Sheaff, Michael
Arthur, Kenneth
Gray, Steven G
O'Byrne, Kenneth J
Richard, Derek J
Soltermann, Alex
Opitz, Isabelle
Pass, Harvey
Harkin, D Paul
Quinn, Jennifer E
Fennell, Dean A
Titel
BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma
Ist Teil von
The Journal of pathology, 2012-06, Vol.227 (2), p.200-208
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2012
Quelle
MEDLINE
Beschreibungen/Notizen
The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine‐induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine‐induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down‐regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re‐activation of vinorelbine‐induced apoptosis following re‐expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.3979
Titel-ID: cdi_crossref_primary_10_1002_path_3979
Format
–
Schlagworte
Antineoplastic Agents, Phytogenic - pharmacology
,
Apoptosis - drug effects
,
Biological and medical sciences
,
Biomarkers, Tumor - genetics
,
Biomarkers, Tumor - metabolism
,
BRCA1
,
BRCA1 Protein - genetics
,
BRCA1 Protein - metabolism
,
Cell Line, Tumor
,
Cell Survival - drug effects
,
Dose-Response Relationship, Drug
,
Drug Resistance, Neoplasm - genetics
,
Humans
,
Immunohistochemistry
,
Inhibitory Concentration 50
,
Investigative techniques, diagnostic techniques (general aspects)
,
malignant pleural mesothelioma
,
Medical sciences
,
Mesothelioma - genetics
,
Mesothelioma - metabolism
,
Mesothelioma - pathology
,
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
,
Pleural Neoplasms - genetics
,
Pleural Neoplasms - metabolism
,
Pleural Neoplasms - pathology
,
Pneumology
,
resistance
,
RNA Interference
,
Transfection
,
Tumors of the respiratory system and mediastinum
,
Vinblastine - analogs & derivatives
,
Vinblastine - pharmacology
,
vinorelbine
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