STAT5 is Activated by Epidermal Growth Factor and Induces Proliferation and Invasion in Trophoblastic Cells

Reprod Sci. 2015 Nov;22(11):1358-66. doi: 10.1177/1933719115578923. Epub 2015 Apr 9.

Abstract

Epidermal growth factor (EGF) is expressed by decidual and trophoblast cells and influences manifold cellular functions during embryo implantation. Thus far, signaling of EGF via Signal Transducer and Activator of Transcription 5 (STAT5) has been only partially investigated. STAT5 stimulates proliferation and cell cycle progression in several cell types. Its dysregulation is associated with pregnancy. The aim of this study was to investigate STAT5 activation and function mediated by EGF in 2 trophoblastic cell lines, namely, HTR8/SVneo and JAR. Additionally, expression of STAT5B messenger RNA (mRNA) in trophoblast models has been compared to that of primary cells isolated from term placentas. Our results demonstrate the highest STAT5B mRNA expression in isolated trophoblast cells, lower expression in HTR8/SVneo cells, and the significantly lowest in JAR cells. Moreover, EGF-mediated STAT5 activation increases cell proliferation and viability in both cell lines. The STAT5 knockdown results in significant decrease in cell viability induced by EGF. Only in HTR8/SVneo cells, invasion decreases after STAT5 silencing and this effect cannot be rescued by further addition of EGF. These results demonstrate that STAT5 activated by EGF constitutes an important cascade for the regulation of cell proliferation and invasion in trophoblast cells.

Keywords: EGF; STAT5; trophoblast.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Phosphorylation
  • Pregnancy
  • RNA Interference
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • STAT5 Transcription Factor
  • STAT5B protein, human
  • Epidermal Growth Factor