Prostaglandin E2 (PGE2), which exerts its
functions by binding to four G protein-coupled
receptors (EP1-4), is implicated in
tumorigenesis. Among the four EP receptors,
EP3 is unique in that it exists as alternatively
spliced variants, characterized by differences
in the cytoplasmic C-terminal tail. Although
three EP3 variants á, â and ã have been
described in mice, their functional significance
in regulating tumorigenesis is unknown. In this
study we provide evidence that expressing
murine EP3 á, â and ã receptor variants in
tumor cells reduces to the same degree their
tumorigenic potential in vivo. In addition,
activation of each of the three mEP3 variants
induces enhanced cell-cell contact and reduces
cell proliferation in vitro in a Rho-dependent
manner. Finally, we demonstrate that EP3-
mediated RhoA activation requires the
engagement of the heterotrimeric G protein
G12. Thus, our study provides strong evidence
that selective activation of each of the three
variants of the EP3 receptor suppresses tumor
cell function by activating a G12-RhoA
pathway.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02052008-181005 |
| Date | 06 March 2008 |
| Creators | Macias-Perez, Ines Maria |
| Contributors | Richard Breyer, Richard Peek, Lynn Matrisian, Ambra Pozzi |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02052008-181005/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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