This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Kotani, T. Articles by Kikkawa, F. PubMed PubMed Citation Articles by Kotani, T. Articles by Kikkawa, F.

Activator Protein-2 Impairs the Invasion of a Human Extravillous Trophoblast Cell Line

Departments of Maternal and Perinatal Medicine (T.K., Ak.I., S.S.) and Obstetrics and Gynecology (K.I., E.Y., H.H., F.K.), Nagoya Graduate University School of Medicine, Nagoya 466-8550, Japan; Division of Pathology (T.N.), Clinical Laboratory, Nagoya Graduate University Hospital, Nagoya 466-8560, Japan; Department of Obstetrics and Gynecology (At.I.), Saitama Medical University, Faculty of Medicine, Saitama 350-0495, Japan; and Seven Bell Clinic (S.N.), Inazawa 492-8144, Japan

Address all correspondence and requests for reprints to: Tomomi Kotani, M.D., Ph.D., Department of Maternal and Perinatal Medicine, Nagoya Graduate University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: itoto{at}med.nagoya-u.ac.jp.

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) and AP-2 act as suppressors of tumor invasion. The present study examined the expressions of AP-2 and AP-2 in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2 and AP-2 were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2 or AP-2 into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2 or AP-2 decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2 and AP-2 were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.