| The G protein-coupled receptor 87 is necessary for p53-dependent cell survival in response to genotoxic stress. | |
MedLine Citation:
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PMID: 19602589 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p53 regulates an array of target genes, which mediates p53 tumor suppression by inducing cell cycle arrest, apoptosis, and cell survival. G protein-coupled receptors belong to a superfamily of cell surface molecules and are known to regulate cell proliferation, migration, and survival. Here, we found that G protein-coupled receptor 87 (GPR87) was up-regulated by p53 and by DNA damage in a p53-dependent manner. We also found that p53 directly regulated GPR87 potentially via a p53-responsive element in the GPR87 gene. To investigate the role of GPR87 in the p53 pathway, we generated multiple RKO and MCF7 cell lines in that GPR87 can be inducibly overexpressed or knocked down by a tetracycline-inducible system. We found that overexpression of GPR87 had little effect on cell growth. However, GPR87 knockdown sensitized cancer cells to DNA damage-induced growth suppression via enhanced p53 stabilization and activation. Importantly, the prosurvival activity of GPR87 can be reversed by knockdown of p53. Together, our results suggested that GPR87 is essential for p53-dependent cell survival in response to DNA damage. Thus, due to its expression on the cell surface and its role in cell survival, GPR87 may be explored as a novel therapeutic target for cancer treatment and prevention. |
Authors:
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Yanhong Zhang; Yingjuan Qian; Wenfu Lu; Xinbin Chen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-14 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-31 Completed Date: 2009-09-11 Revised Date: 2014-09-12 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 6049-56 Citation Subset: IM |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Growth Processes
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physiology Cell Line, Tumor DNA Damage* Gene Expression Regulation, Neoplastic* HCT116 Cells Humans RNA, Small Interfering / genetics Receptors, Lysophosphatidic Acid / biosynthesis, genetics* Reverse Transcriptase Polymerase Chain Reaction Transfection Tumor Suppressor Protein p53 / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA076069/CA/NCI NIH HHS; CA102188/CA/NCI NIH HHS; R01 CA076069/CA/NCI NIH HHS; R01 CA076069-14/CA/NCI NIH HHS; R01 CA102188/CA/NCI NIH HHS; R01 CA102188-08/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GPR87 protein, human; 0/RNA, Small Interfering; 0/Receptors, Lysophosphatidic Acid; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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