Biomedical Engineering Reference
In-Depth Information
density (e.g., heart and breast tissue). Studies by Scheffer et al.
125
and Faneyte et al.
126
also found expression in breast tissue to localize to the vascular endothelium rather
than normal mammary or breast cancer tissue. Directing a specially generated poly-
clonal rabbit ABCG2 antibody (termed 405) against an 18-mer peptide near the ATP-
binding region together with the commercially available 5D3 monoclonal antibody,
we also found high expression of this protein in the syncytiotrophoblast placenta,
alveolar pneumocytes in the lung, skin sebaceous glands, small and large intestine,
bile canaliculi, and blood vessels, including endothelium from the central nervous
system.
123
12.8. FUNCTION PREDICTED FROM TISSUE DISTRIBUTION
The location and level of expression of ABCG2 highlight the protein's potential roles
in the normal host. These include probable roles in protecting stem cells; forming
the maternal-fetal barrier, the blood-testis cell barrier, and the blood-brain barrier;
and its role in the absorption and efflux of xenobiotics and endogenous metabolic
products within the gastrointestinal tract.
12.8.1. Stem Cells
Recent evidence has shown that ABCG2 may play a critical role in the phenotype of
stem cells. Hematopoietic stem cells can be recognized as a
side population
(SP), when
bone marrow cells are studied via flow cytometry. These SP cells extrude Hoechst
33342 and have surface antigen expression profiles that correspond to a stem cell
phenotype.
127
Hoescht 33342 is a known substrate for ABCB1, but after investigators
found no differences in the SP cell population in ABCB1-deficient and wild-type
mice,
82
Zhou et al. reported that ABCG2 was responsible for the SP phenotype. High
levels of ABCG2, which also effluxes Hoechst dye, were found in early murine stem
cells, including hematopoietic, muscle, and embryonic stem cells, potentially protect-
ing the cell from exogenous toxins or serving an unknown function in endogenous
substrate efflux. As these cells matured, ABCG2 levels subsided, and other efflux
mechanisms, such as ABCB1, were up-regulated. Although ABCG2 may serve as
part of the stem cell phenotype, it is neither necessary nor sufficient for stem cell de-
velopment and cellular differentiation, a fact confirmed by the observation that there is
no significant developmental pathology associated with
Abcg2
-deficient mice. Since
Zhou's publication, ABCG2 has been identified as a potential phenotypic marker for
stem cells in multiple tissues, including normal lung
128
and breast tissue.
129
12.8.2. Placenta
ABCG2 may function in the human placenta to protect the fetus or to transport
steroid hormones produced in the placenta.
130
Specifically, E
1
S and DHEAS are
among the major estrogens produced and secreted by the placenta, and as shown
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