Regulation of the angiopoietin-2 gene by hCG in ovarian cancer cell line OVCAR-3

Horm Metab Res. 2010 May;42(5):328-33. doi: 10.1055/s-0030-1249021. Epub 2010 Mar 8.


Angiogenesis is a crucial step in growing tissues including many tumors. It is regulated by pro- and antiangiogenic factors including the family of angiopoietins and their corresponding receptors. In previous work we have shown that in human ovarian cells the expression of angiopoietin 2 (ANG2) is regulated by human chorionic gonadotropin (hCG). To better understand the mechanisms of hCG-dependent regulation of the ANG2-gene we have now investigated upstream regulatory active elements of the ANG2-promoter in the ovarian carcinoma cell line OVCAR-3. We cloned several ANG2-promoter-fragments of different lengths into a luciferase reporter-gene-vector and analyzed the corresponding ANG2 expression before and after hCG stimulation. We identified regions of the ANG2-promoter between 1 048 bp and 613 bp upstream of the transcriptional start site where hCG-dependent pathways promote a significant downregulation of gene expression. By sequence analysis of this area we found several potential binding sites for transcription factors that are involved in regulation of ANG2-expression, vascular development and ovarian function. These encompass the forkhead family transcription factors FOXC2 and FOXO1 as well as the CCAAT/enhancer binding protein family (C/EBP). In conclusion, we have demonstrated that the regulation of ANG2-expression in ovarian cancer cells is hCG-dependent and we suggest that forkhead transcription factor and C/EBP-dependent pathways are involved in the regulation of ANG2-expression in ovarian cancer cells.

MeSH terms

  • Angiopoietin-2 / genetics*
  • Cell Line, Tumor
  • Chorionic Gonadotropin / physiology*
  • Cloning, Molecular
  • DNA Primers
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Luteinizing Hormone / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Promoter Regions, Genetic / genetics
  • Receptors, LH / biosynthesis
  • Receptors, LH / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • Angiopoietin-2
  • Chorionic Gonadotropin
  • DNA Primers
  • Forkhead Transcription Factors
  • Receptors, LH
  • Luteinizing Hormone