| Summary: | 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.
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