dc.creator | Macias-Perez, Ines Maria | |
dc.date.accessioned | 2020-08-21T20:59:32Z | |
dc.date.available | 2010-03-06 | |
dc.date.issued | 2008-03-06 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-02052008-181005 | |
dc.identifier.uri | http://hdl.handle.net/1803/10528 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | GPCR | |
dc.subject | EP receptor | |
dc.subject | Prostaglandins -- Receptors | |
dc.subject | Cyclooxygenase 2 | |
dc.subject | Colon (Anatomy) -- Cancer -- Molecular aspects | |
dc.title | The role of the murine EP3 receptor variants on cell function. | |
dc.type | dissertation | |
dc.contributor.committeeMember | Richard Breyer | |
dc.contributor.committeeMember | Richard Peek | |
dc.contributor.committeeMember | Lynn Matrisian | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cancer Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2010-03-06 | |
local.embargo.lift | 2010-03-06 | |
dc.contributor.committeeChair | Ambra Pozzi | |