Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein‐2 in BeWo cell model of human trophoblast differentiation

FEBS Letters

Itakura, Atsuo²  Tsujimoto, Masafumi¹  Kikkawa, Fumitaka²  Nomura, Seiji²  Okada, Mayumi²  Yamamoto, Eiko²  Ito, Tomomi²  Ikoma, Yoko²  Iwanaga, Kumi²  Mizutani, Shigehiko² 

[1] Laboratory of Cellular Biochemistry, RIKEN, Wako 351-0198, Japan;Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan

关键词: Aminopeptidase;    Cell differentiation;    Gene regulation;    Oxytocin;    Placenta;    P-LAP;    placental leucine aminopeptidase;    FSK;    forskolin;    AP-2;    activator protein-2;   

DOI  :  10.1016/S0014-5793(03)00897-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown