STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas

Autor: Daniel Vaiman, Franck Letourneur, Virginie Rigourd, R. Rebourcet, Sonia T. Chelbi, Thérèse-Marie Mignot, Sandrine Barbaux, Françoise Mondon, Caroline Chauvet
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Chromatin Immunoprecipitation
medicine.medical_specialty
Transcription
Genetic
Placenta
Obstetrics/Hypertensive Disorders
lcsh:Medicine
Biology
medicine.disease_cause
Preeclampsia
Transcriptome
Pre-Eclampsia
Pregnancy
Cell Line
Tumor
Internal medicine
medicine
Cluster Analysis
Humans
Choriocarcinoma
Promoter Regions
Genetic
lcsh:Science
Transcription factor
Cell Biology/Gene Expression
reproductive and urinary physiology
Binding Sites
Multidisciplinary
Genetics and Genomics/Functional Genomics
Molecular Mimicry
lcsh:R
Transfection
medicine.disease
Gene Expression Regulation
Neoplastic
Molecular mimicry
Endocrinology
medicine.anatomical_structure
Immunology
embryonic structures
Regression Analysis
Female
lcsh:Q
Carrier Proteins
Chromatin immunoprecipitation
Genes
Neoplasm
Transcription Factors
Research Article
Zdroj: PLoS ONE, Vol 3, Iss 12, p e3905 (2008)
PLoS ONE
ISSN: 1932-6203
Popis: 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. METHODOLOGY AND PRINCIPAL FINDINGS: 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.
Databáze: OpenAIRE
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