| Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades. | |
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MedLine Citation:
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PMID: 19725049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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cAMP-dependent, PKA-independent effects on cell proliferation are mediated by cAMP binding to EPAC and activation of Rap signaling. In this report, we employed the analogue 8-CPT-2-O-Me-cAMP to study binding to EPAC and subsequent activation of B-Raf/ERK and mTOR signaling in human cancer cells. This compound significantly stimulated DNA synthesis, protein synthesis, and cellular proliferation of human 1-LN prostate cancer cells. By study of phosphorylation-dependent activation, we demonstrate that EPAC-mediated cellular effects require activation of the B-Raf/ERK and mTOR signaling cascades. RNAi directed against EPAC gene expression as well as inhibitors of ERK, PI 3-kinase, and mTOR were employed to further demonstrate the role of these pathways in regulating prostate cancer cell proliferation. These studies were then extended to several other human prostate cancer cell lines and melanoma cells with comparable results. We conclude that B-Raf/ERK and mTOR signaling play an essential role in cAMP-dependent, but PKA-independent, proliferation of cancer cells. |
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Authors:
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Uma Kant Misra; Salvatore Vincent Pizzo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 108 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-26 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 998-1011 Citation Subset: IM |
Copyright Information:
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(c) 2009 Wiley-Liss, Inc. |
Affiliation:
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Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Proliferation Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Inhibitors / pharmacology Extracellular Signal-Regulated MAP Kinases / metabolism* Guanine Nucleotide Exchange Factors / metabolism* Humans Intracellular Signaling Peptides and Proteins / metabolism* Male Phosphorylation Prostatic Neoplasms / metabolism* Protein-Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins B-raf / metabolism* Signal Transduction Theophylline / analogs & derivatives, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA 131235-01A2/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Guanine Nucleotide Exchange Factors; 0/Intracellular Signaling Peptides and Proteins; 0/RAPGEF3 protein, human; 35873-49-5/8-cyclopentyl-1,3-dimethylxanthine; 58-55-9/Theophylline; 60-92-4/Cyclic AMP; EC 2.7.1.-/mTOR protein; EC 2.7.1.37/BRAF protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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