Expression of TGF-beta signaling genes in the normal, premalignant, and malignant human trophoblast: loss of smad3 in choriocarcinoma cells

Biochem Biophys Res Commun. 2001 Sep 14;287(1):47-55. doi: 10.1006/bbrc.2001.5533.

Abstract

We had earlier shown that TGF-beta controls proliferation, migration, and invasiveness of normal human trophoblast cells, whereas premalignant and malignant trophoblast cells are resistant to TGF-beta. To identify signaling defects responsible for TGF-beta resistance in premalignant and malignant trophoblasts, we have compared the expression of TGF-beta signaling molecules in a normal trophoblast cell line (HTR-8), its premalignant derivative (RSVT2/C), and two choriocarcinoma cell lines (JAR and JEG-3). RT-PCR analysis revealed that all these cell lines expressed the mRNA of TGF-beta1, -beta2, and -beta3, TGF-beta receptors type I, II, and III, and post-receptor signaling genes smad2, smad3, smad4, smad6, and smad7 with the exception that TGF-beta2 and smad3 were undetectable in JAR and JEG-3 cells. Immunoblot analysis confirmed the absence of smad3 protein in choriocarcinoma cells. Treatment with TGF-beta1 induced smad3 phosphorylation and smad3 translocation to the nucleus in the normal and premalignant trophoblast cells. These results suggest that loss of smad3 may account for a functional disruption in the TGF-beta signaling pathway in choriocarcinomas, but not in the premalignant trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Choriocarcinoma / genetics
  • Choriocarcinoma / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Phosphorylation
  • Pregnancy
  • Signal Transduction
  • Smad3 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Trophoblastic Neoplasms / genetics
  • Trophoblastic Neoplasms / metabolism*
  • Trophoblasts / metabolism*
  • Tumor Cells, Cultured
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism

Substances

  • DNA-Binding Proteins
  • SMAD3 protein, human
  • Smad3 Protein
  • Trans-Activators
  • Transforming Growth Factor beta