STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.
BACKGROUND
Mutations in STOX1 were proposed to be causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation.


RESULTS
In the present study, we have produced a choriocarcinoma cell line overexpressing STOX1. This overexpression results in transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r = 0.30, p = 9.10(-7)). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chorionic gonadotrophin -hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells.


CONCLUSIONS
Our results contribute to reconcile contradictory data concerning the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Our cellular model could constitute an invaluable resource for studying specific aspects of this human disease.
Rigourd
Virginie
V
Equipe 21, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Chauvet
Caroline
C
Chelbi
Sonia T
ST
Rebourcet
Régis
R
Mondon
Françoise
F
Letourneur
Franck
F
Mignot
Thérèse-Marie
TM
Barbaux
Sandrine
S
Vaiman
Daniel
D
D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D018716:Molecular Mimicry / Q000235:genetics*; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; C500784:STOX1 protein, human; D014157:Transcription Factors