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Horm Metab Res 2010; 42(5): 328-333
DOI: 10.1055/s-0030-1249021
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Regulation of the Angiopoietin-2 Gene by hCG in Ovarian Cancer Cell Line OVCAR-3

D. Pietrowski[*] 1 , 3 , P. Wiehle[*] 2 , M. Sator1 , 3 , A. Just1 , 3 , C. Keck4
  • 1Department for Obstetrics and Gynecology, Medical University Vienna, Vienna, Austria
  • 2Department for Obstetrics and Gynecology, University Medical School Freiburg, Freiburg, Germany
  • 3Fertilitätszentrum Döbling, Vienna, Austria
  • 4Pan Klinik Köln, Cologne, Germany
Further Information

Publication History

received 23.09.2009

accepted 02.02.2010

Publication Date:
08 March 2010 (online)

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Abstract

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.

Key words

gonadotropin - angiopoietin - cancer - angiogenesis

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1 These authors contributed equally to this work.

Correspondence

D. Pietrowski

Medizinische Universität Wien

Waehringer Guertel 18–20

1090 Wien

Austria

Phone: +43/40/400 2897

Fax: +43/40/400 3016

Email: detlef.pietrowski@meduniwien.ac.at

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