Document Detail

Regulator of G-protein signalling expression and function in ovarian cancer cell lines.
MedLine Citation:
PMID:  18979070     Owner:  NLM     Status:  MEDLINE    
Regulator of G-protein signalling (RGS)(2) proteins critically regulate signalling cascades initiated by G-protein coupled receptors (GPCRs) by accelerating the deactivation of heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is the predominant growth factor that drives the progression of ovarian cancer by activating specific GPCRs and G-proteins expressed in ovarian cancer cells. We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling. The goal of this study was twofold: first, to identify candidate RGS proteins expressed in SKOV-3 cells that may account for the reported negative regulation of G-protein signalling, and second, to determine if these RGS protein transcripts are differentially expressed among commonly utilized ovarian cancer cell lines and non-cancerous ovarian cell lines. Reverse transcriptase-PCR was performed to determine transcript expression of 22 major RGS subtypes in RNA isolated from SKOV-3, OVCAR-3 and Caov-3 ovarian cancer cell lines and non-cancerous immortalized ovarian surface epithelial (IOSE) cells. Fifteen RGS transcripts were detected in SKOV-3 cell lines. To compare the relative expression levels in these cell lines, quantitative real time RT-PCR was performed on select transcripts. RGS19/GAIP was expressed at similar levels in all four cell lines, while RGS2 transcript was detected at levels slightly lower in ovarian cancer cells as compared to IOSE cells. RGS4 and RGS6 transcripts were expressed at dramatically different levels in ovarian cancer cell lines as compared to IOSE cells. RGS4 transcript was detected in IOSE at levels several thousand fold higher than its expression level in ovarian cancer cells lines, while RGS6 transcript was expressed fivefold higher in SKOV-3 cells as compared to IOSE cells, and over a thousand fold higher in OVCAR-3 and Caov-3 cells as compared to IOSE cells. Functional studies of RGS 2, 6, and 19/GAIP were performed by measuring their effects on LPA stimulated production of inositol phosphates. In COS-7 cells expressing individual exogenous LPA receptors, RGS2 and RSG19/GAIP attenuated signalling initiated by LPA1, LPA2, or LPA3, while RGS6 only inhibited signalling initiated by LPA2 receptors. In SKOV-3 ovarian cancer cells, RGS2 but not RGS6 or RGS19/GAIP, inhibited LPA stimulated inositol phosphate production. In contrast, in CAOV-3 cells RGS19/GAIP strongly attenuated LPA signalling. Thus, multiple RGS proteins are expressed at significantly different levels in cells derived from cancerous and normal ovarian cells and at least two candidate RGS transcripts have been identified to account for the reported regulation of LPA signalling pathways in ovarian cancer cells.
Jillian H Hurst; Nisha Mendpara; Shelley B Hooks
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-31
Journal Detail:
Title:  Cellular & molecular biology letters     Volume:  14     ISSN:  1689-1392     ISO Abbreviation:  Cell. Mol. Biol. Lett.     Publication Date:  2009  
Date Detail:
Created Date:  2008-12-24     Completed Date:  2009-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607427     Medline TA:  Cell Mol Biol Lett     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  153-74     Citation Subset:  IM    
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
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MeSH Terms
COS Cells
Cell Line, Tumor
Cercopithecus aethiops
Gene Expression Regulation, Neoplastic
Inositol Phosphates / metabolism
Ovarian Neoplasms / genetics,  metabolism*
RGS Proteins / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Receptors, Lysophosphatidic Acid / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Reg. No./Substance:
0/Inositol Phosphates; 0/RGS Proteins; 0/RNA, Messenger; 0/Receptors, Lysophosphatidic Acid

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