Abstract
Bfl-1 is a pro-survival Bcl-2 family member overexpressed in a subset of chemoresistant tumours, including melanoma. Here, we characterised the expression and regulation of Bfl-1 in normal and malignant melanocytes and determined its role in protecting these cells from chemotherapy-induced apoptosis. Bfl-1 was mitochondrially resident in both resting and apoptotic cells and experienced regulation by the proteasome and NFκB pathways. siRNA-mediated knockdown enhanced sensitivity towards various relevant drug treatments, with forced overexpression of Bfl-1 protective. These findings identify Bfl-1 as a contributor towards therapeutic resistance in melanoma cells and support the use of NFκB inhibitors alongside current treatment strategies.
Keywords:
Apoptosis; BCL2A1; Bfl-1; Melanocytes; Melanoma.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / genetics
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Cell Line, Tumor
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Cell Survival
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Cells, Cultured
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Cytoprotection
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Melanocytes / metabolism
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Melanoma / genetics
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Melanoma / metabolism*
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Melanoma / pathology*
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Minor Histocompatibility Antigens
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Mitochondria / metabolism
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Mutation / genetics
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NF-kappa B / metabolism
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Proteasome Endopeptidase Complex / metabolism
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Proteolysis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction / genetics
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Skin Neoplasms / genetics
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Skin Neoplasms / metabolism*
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Skin Neoplasms / pathology*
Substances
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BCL2-related protein A1
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Minor Histocompatibility Antigens
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Proteasome Endopeptidase Complex