Document Detail


The G protein-coupled receptor 87 is necessary for p53-dependent cell survival in response to genotoxic stress.
MedLine Citation:
PMID:  19602589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yanhong Zhang; Yingjuan Qian; Wenfu Lu; Xinbin Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-07-14
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-31     Completed Date:  2009-09-11     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6049-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Growth Processes / 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:
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:
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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