Transcription Factor AP-2α Promotes EGF-Dependent Invasion of Human Trophoblast

• DOI: 10.1210/en.2010-0936
• Publication Date: 2011-02-09T03:05:55Z
• Authors: Katarzyna Biadasi...; Stefan Sonderegger; Peter Haslinger; Sandra Haider; Leila Saleh; Christian Fiala; Jürgen Pollheimer; Martin Knöfler
• Keywords: Matrigel; Trophoblast

The basic helix-span-helix transcription factor activating protein (AP)-2α is critically involved in cell-specific hormone expression of syncytializing human trophoblasts. Its role invasive trophoblast differentiation, however, remains largely elusive. Using RT-PCR, Western blotting, and immunofluorescence first-trimester placentae, we here show that AP-2α expressed extravillous trophoblasts (EVTs) both situ vitro as well cell lines. was increased upon supplementation epidermal growth (EGF) primary EVTs trophoblastic SGHPL-5 cells. Gene silencing using small hairpin microRNA (shRNAmir) did not affect basal invasion cells through Matrigel-coated filters but reduced EGF-stimulated invasion. Similarly, treatment with interfering RNA decreased EGF-dependent Proliferation EVTs, measured by cumulative numbers 5-bromo-2'-deoxyuridine labeling, respectively, were affected on loss AP-2α. induction matrix metalloproteinase (MMP)-2, pro- active form urokinase plasminogen activator, chorionic gonadotropin (CG)-β noticed shRNAmir-control cells, whereas these genes suppressed EGF-treated shRNAmir-AP-2α MMP-2 CGβ RNA-treated EVTs. Knockdown also luciferase activity the CGβ5 promoter which compensated transient overexpression cDNA. In conclusion, positively affects under conditions, likely inducing critical invasion-promoting such MMP-2, CG.