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Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein‐2 in BeWo cell model of human trophoblast differentiation
Author(s) -
Iwanaga Kumi,
Nomura Seiji,
Ito Tomomi,
Ikoma Yoko,
Yamamoto Eiko,
Okada Mayumi,
Itakura Atsuo,
Kikkawa Fumitaka,
Tsujimoto Masafumi,
Mizutani Shigehiko
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00897-4
Subject(s) - syncytiotrophoblasts , forskolin , activator (genetics) , biology , luciferase , microbiology and biotechnology , trophoblast , transfection , cell culture , endocrinology , medicine , placenta , biochemistry , gene , fetus , genetics , pregnancy
Placental leucine aminopeptidase (P‐LAP) is located preferentially in syncytiotrophoblasts in human placenta. Here we investigated P‐LAP expression and the regulatory mechanisms in BeWo choriocarcinoma cells with forskolin (FSK)‐induced differentiation. Morphologically differentiated cells revealed enhanced P‐LAP staining. FSK significantly increased P‐LAP activity and mRNA. Deletion or mutation of activator protein‐2 (AP‐2) binding site in the footprint‐3 (−216 to −172) of P‐LAP promoter abrogated the stimulatory effects of FSK on luciferase activity of the construct −216/+49. In AP‐2‐deficient Hep‐G2 cells, FSK failed to stimulate luciferase activity of the construct −216/+49. Among the isoforms, BeWo expressed AP‐2α and AP‐2γ, while FSK increased only AP‐2α. These results suggest differentiation‐dependent P‐LAP expression in trophoblasts, which involves increased AP‐2α binding.