Abstract
HER-2/neu has been implicated in the activation of androgen receptor (AR) and in inducing hormone-independent prostate cancer growth. Here we report that HER-2/neu activates Akt (protein kinase B) to promote prostate cancer cell survival and growth in the absence of androgen. Blocking of the Akt pathway by a dominant-negative Akt or an inhibitor LY294002 abrogates the HER-2/neu-induced AR signaling and cell survival/growth effects in the absence or presence of androgen. Akt specifically binds to AR and phosphorylates serines 213 and 791 of AR. Thus, Akt is a novel activator of AR required for HER-2/neu signaling to androgen-independent survival and growth of prostate cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Western
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Cell Division
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Cell Line
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Cell Survival / drug effects
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Chromones / pharmacology
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Genes, Dominant
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Genes, Reporter
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Humans
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Male
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Mice
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Models, Biological
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Molecular Sequence Data
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Morpholines / pharmacology
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Phosphorylation
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Precipitin Tests
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Prostatic Neoplasms / metabolism*
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Protein Binding
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Rats
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Receptor, ErbB-2 / metabolism*
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Sequence Homology, Amino Acid
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Serine / metabolism
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Signal Transduction
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Tumor Cells, Cultured
Substances
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Chromones
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Enzyme Inhibitors
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Morpholines
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Proto-Oncogene Proteins
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Serine
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Receptor, ErbB-2
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AKT1 protein, human
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt