Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein-2 in BeWo cell model of human trophoblast differentiation.
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-2alpha and AP-2gamma, while FSK increased only AP-2alpha. These results suggest differentiation-dependent P-LAP expression in trophoblasts, which involves increased AP-2alpha binding.
Iwanaga
Kumi
K
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Nomura
Seiji
S
Ito
Tomomi
T
Ikoma
Yoko
Y
Yamamoto
Eiko
E
Okada
Mayumi
M
Itakura
Atsuo
A
Kikkawa
Fumitaka
F
Tsujimoto
Masafumi
M
Mizutani
Shigehiko
S
D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D010122:Cystinyl Aminopeptidase / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D008954:Models, Biological; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C493673:TFAP2A protein, human; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D005576:Colforsin; D008156:Luciferases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase