research day - University of Toronto Department of Obstetrics and ...

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ABSTRACT #P-L1
EXPRESSION AND REGULATION OF BREAST CANCER RESISTANCE PROTEIN
(BCRP1) IN THE MOUSE PLACENTA AND FETAL BLOOD-BRAIN BARRIER
Sophie Petropoulos [G](1), A Kostaki(1), W Gibb(4), SG Matthews(1)(2)(3). Departments of
(1)Physiology, (2)Obstetrics and Gynaecology, (3)Medicine, University of Toronto; Departments
of (4)Obstetrics and Gynecology, Cellular and Molecular Medicine, University of Ottawa.
Objective: Human Breast Cancer Resistance Protein (BCRP) is an active efflux transporter with a
wide range of substrates including xenobiotics (chemotherapeutic agents and therapeutic drugs)
and endobiotics (folic acid and steroids). In both the human and mouse, we have recently shown
that Bcrp1 is localized in the placental labyrinth. In the mouse, Bcrp1 mRNA is highly expressed
at mid-gestation, but dramatically declines towards term. Such changes in expression correspond
to increasing levels of circulating glucocorticoid concentrations, indicating a possible role in the
regulation of Bcrp1 expression. In the mouse, we have also localized Bcrp1 in the fetal blood-brain
barrier (BBB) in late gestation, however, nothing is known regarding its ontogenic expression.
Further, information pertaining to the regulation of Bcrp1 in both the placenta and fetal BBB is
non-existent. In this study, we hypothesize that; 1) Bcrp1 expression in the fetal BBB will increase
with advancing gestation, providing local protection to the developing brain at this time. 2)
Synthetic glucocorticoid administration will down-regulate placental Bcrp1 and up-regulate Bcrp1
expression in the BBB.
Methods: Pregnant FVB mice were treated with either DEX (1mg/kg) or vehicle from either
embryonic day (E)9.5-15.5 or E12.5-E18.5. On E15.5 or E18.5, dams were euthanized and
placentas and fetal brains collected. Total RNA and protein was extracted using TRIzol.
Expression of Bcrp1 mRNA and protein were measured by real-time RT PCR and Western
analysis respectively.
Results: We have now shown that expression of Bcrp1 mRNA in the fetal BBB significantly
(P