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Title page for ETD etd-02052008-181005


Type of Document Dissertation
Author Macias-Perez, Ines Maria
URN etd-02052008-181005
Title The role of the murine EP3 receptor variants on cell function.
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Ambra Pozzi Committee Chair
Lynn Matrisian Committee Member
Richard Breyer Committee Member
Richard Peek Committee Member
Keywords
  • GPCR
  • EP receptor
  • Prostaglandins -- Receptors
  • Cyclooxygenase 2
  • Colon (Anatomy) -- Cancer -- Molecular aspects
Date of Defense 2007-12-04
Availability unrestricted
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.

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