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rdf:type |
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lifeskim:mentions |
umls-concept:C0015744,
umls-concept:C0034786,
umls-concept:C0044602,
umls-concept:C0285761,
umls-concept:C0376358,
umls-concept:C0851285,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1514762,
umls-concept:C1705325,
umls-concept:C1882911,
umls-concept:C2911691
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pubmed:issue |
5
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pubmed:dateCreated |
2011-5-17
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pubmed:databankReference |
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pubmed:abstractText |
Prostate cancer is characterized by its dependence on androgen receptor (AR) and frequent activation of PI3K signaling. We find that AR transcriptional output is decreased in human and murine tumors with PTEN deletion and that PI3K pathway inhibition activates AR signaling by relieving feedback inhibition of HER kinases. Similarly, AR inhibition activates AKT signaling by reducing levels of the AKT phosphatase PHLPP. Thus, these two oncogenic pathways cross-regulate each other by reciprocal feedback. Inhibition of one activates the other, thereby maintaining tumor cell survival. However, combined pharmacologic inhibition of PI3K and AR signaling caused near-complete prostate cancer regressions in a Pten-deficient murine prostate cancer model and in human prostate cancer xenografts, indicating that both pathways coordinately support survival.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Androgen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Myc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PHLPP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Pten protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Androgen
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1878-3686
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pubmed:author |
pubmed-author:AroraVivek KVK,
pubmed-author:CarverBrett SBS,
pubmed-author:ChandarlapatySaratS,
pubmed-author:ChapinskiCarenC,
pubmed-author:FengZ PZP,
pubmed-author:HieronymusHaleyH,
pubmed-author:KoutcherJasonJ,
pubmed-author:LeCarlC,
pubmed-author:RosenNealN,
pubmed-author:SawyersCharles LCL,
pubmed-author:ScardinoPeter TPT,
pubmed-author:ScherHowardH,
pubmed-author:WongvipatJohnJ
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
17
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
575-86
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pubmed:dateRevised |
2011-7-26
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pubmed:meshHeading |
pubmed-meshheading:21575859-Androgen Antagonists,
pubmed-meshheading:21575859-Animals,
pubmed-meshheading:21575859-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:21575859-Cell Line, Tumor,
pubmed-meshheading:21575859-Cell Proliferation,
pubmed-meshheading:21575859-Feedback, Physiological,
pubmed-meshheading:21575859-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21575859-Genes, Reporter,
pubmed-meshheading:21575859-Humans,
pubmed-meshheading:21575859-Magnetic Resonance Imaging,
pubmed-meshheading:21575859-Male,
pubmed-meshheading:21575859-Mice,
pubmed-meshheading:21575859-Mice, Knockout,
pubmed-meshheading:21575859-Mice, SCID,
pubmed-meshheading:21575859-Mice, Transgenic,
pubmed-meshheading:21575859-Nuclear Proteins,
pubmed-meshheading:21575859-PTEN Phosphohydrolase,
pubmed-meshheading:21575859-Phosphatidylinositol 3-Kinase,
pubmed-meshheading:21575859-Phosphoprotein Phosphatases,
pubmed-meshheading:21575859-Prostatic Neoplasms,
pubmed-meshheading:21575859-Protein Kinase Inhibitors,
pubmed-meshheading:21575859-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21575859-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:21575859-RNA Interference,
pubmed-meshheading:21575859-Receptor, erbB-2,
pubmed-meshheading:21575859-Receptor, erbB-3,
pubmed-meshheading:21575859-Receptors, Androgen,
pubmed-meshheading:21575859-Signal Transduction,
pubmed-meshheading:21575859-Time Factors,
pubmed-meshheading:21575859-Transcription, Genetic,
pubmed-meshheading:21575859-Transfection,
pubmed-meshheading:21575859-Tumor Burden,
pubmed-meshheading:21575859-Xenograft Model Antitumor Assays
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pubmed:year |
2011
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pubmed:articleTitle |
Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer.
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