Abstract
To dissect the isoform-specific roles of Akt in breast cancer cells, constitutively active Akt isoforms were introduced into MDA-MB-231 cells. Both Akt1 and Akt2 efficiently inhibited the growth of MDA-MB-231 cells. Overexpression of Akt1 down-regulated ERK activity inhibiting Ser 259 phosphorylation of c-Raf and subsequent downstream signaling. Akt2 overexpression up-regulated the cell cycle inhibitor p27. Cycloheximide decay assays showed that Akt2 increased the stability and nuclear localization of p27, thus inhibiting the cyclin E/CDK2 complex. These results suggest that the inhibition of cell proliferation by Akt1 and Akt2 is mediated by isoform-specific mechanisms.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / enzymology
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Breast Neoplasms / metabolism
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Cell Line, Tumor
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Cell Proliferation
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Cyclin E / metabolism
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Cyclin-Dependent Kinase 2 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Humans
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Phosphorylation
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Proto-Oncogene Proteins c-raf / metabolism
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Signal Transduction
Substances
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Cyclin E
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Protein Isoforms
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Cyclin-Dependent Kinase Inhibitor p27
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Extracellular Signal-Regulated MAP Kinases