We showed previously that the selenium-dependent glutathione peroxidase, GP
X-GI, encoded by the Gpx2 gene, is highly expressed in the epithelium of th
e gastrointestinal (GI) tract and sporadically in breast tissue, To investi
gate whether Gpx2 gene expression is epithelium specific, we used in situ h
ybridization to show that Gpx2 mRNA is highly expressed in the crypt epithe
lium of human intestine. We also used Northern analysis to study human brea
st cells and found Gpx2 mRNA in human mammary epithelial cell lines as well
as freshly isolated normal breast epithelial cells, Because we identified
three putative retinoic acid response elements (RARE) in the Gpx2 gene, we
examined the regulation of the Gpx2 gene expression by all-trans retinoic a
cid (RA) in RA-sensitive MCF-7 cells and RA-resistant HT29 cells. Without R
A, MCF-7 cells had very low levels of Gpx2 mRNA and a low level of glutathi
one peroxidase (GPX) activity (17 mU/mg protein), whereas HT29 cells had a
high level of Gpx2 mRNA and GPX activity (200 mU/mg protein). RA treatment
increased Gpx2 mRNA level 3- to 11-fold and resulted in a fourfold increase
of GPX activity (80 mU/mg protein) in MCF-7 cells. Neither Gpx2 mRNA level
nor GPX activity was increased in HT29 cells, These results show that the
Gpx2 gene is expressed in both breast and intestinal epithelium cells, and
suggest that its expression can be highly regulated by retinoic acid, a kno
wn differentiation agent.