Abstract
The expression of Nuclear Protein 1 (NUPR1) is associated with chemoresistance in multiple malignancies. We previously reported that NUPR1 functions as a transcriptional cofactor for the p300-p53 complex and transcriptionally regulates p21 expression. In the present study we investigated the activity of NUPR1 in p53-deficient, triple-negative, inflammatory SUM159 breast cancer cells. Our studies reveal that NUPR1 confers growth benefit and chemoresistance by causing Akt-mediated phosphorylation and subsequent cytoplasmic re-localization of p21 and activation of the anti-apoptotic Bcl-xL protein. Our findings elucidate a NUPR1-PI-3-K/Akt-phospho-p21 axis that functions in p53-negative, inflammatory breast cancer cells to enhance chemoresistance in breast cancer.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Biological Transport, Active
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Cytoplasm / metabolism
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Doxorubicin / pharmacology
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Drug Resistance, Neoplasm / physiology*
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Female
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Humans
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / metabolism
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Oncogene Protein v-akt / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Signal Transduction
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Tumor Suppressor Protein p53 / metabolism
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bcl-X Protein / metabolism
Substances
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BCL2L1 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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NUPR1 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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bcl-X Protein
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Doxorubicin
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Oncogene Protein v-akt