Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.
BACKGROUND
Preeclampsia is an important clinical condition with unknown etiology. We used DNA array technique to compare placental gene expression profile in severe early-onset preeclampsia from 25 to 27 gestational weeks with strictly non-affected placental samples from similar gestational weeks.


METHODS
DNA arrays were validated by showing the up-regulation of several genes typical for preeclampsia such as chorionic gonadotrophin beta-chain, tissue factor pathway inhibitor, and intercellular adhesion molecule-1. In DNA array, 5% of genes displayed less than or equal to twofold increase in expression level and only 0.2% of genes showed < or =0.5-fold decrease in expression in preeclampsia versus control. Signs of immunological factors, hypoxia, apoptosis, oxidative stress and altered thrombosis, coagulation as well as endothelial injury were seen in the gene expression profile.


RESULTS
As a new finding, we identified a group of 13 genes with a function in tumor suppression and growth regulation which were significantly up-regulated in preeclampsia. Three out of the five most highly up-regulated genes belonged to this group which included genes, such as protein phosphatase 2, phospholipid scramblase 1, transcription elongation factor, melanoma adhesion molecule, retinoic acid receptor responder 3, and RANTES.


CONCLUSIONS
It is concluded that up-regulation of tumor suppressor and growth regulatory genes may play an important role in the pathogenesis of severe early-onset preeclampsia.
Heikkilä
Annaleena
A
A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland.
Tuomisto
Tiina
T
Häkkinen
Sanna-Kaisa
SK
Keski-Nisula
Leea
L
Heinonen
Seppo
S
Ylä-Herttuala
Seppo
S
D000328:Adult; D002585:Cesarean Section; D005260:Female; D020869:Gene Expression Profiling; D005809:Genes, Regulator; D016147:Genes, Tumor Suppressor; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D015854:Up-Regulation