1. ¹Department of Clinical Research, University of Bern, Bern, Switzerland
2. ²Department of Hematology and Oncology, Charité, Campus Benjamin Franklin-Klinikum, University Medicine Berlin, Berlin, Germany
3. ³Department of Medical Oncology, University Hospital, Bern, Switzerland

Correspondence: Dr S Aebi, Department of Medical Oncology, University Hospital Inselspital, 3010 Bern, Switzerland. E-mail: stefan.aebi@insel.ch

Received 23 February 2005; Revised 27 May 2005; Accepted 23 June 2005; Published online 23 August 2005.

Abstract

Elements of the Notch pathway regulate differentiation; we investigated the expression of such elements in epithelial ovarian tumours. A total of 32 ovarian tumour samples (17 adenocarcinomas, three borderline tumours, 12 adenomas), two human ovarian cancer (A2780, OVCAR3), and one ovarian surface (IOSE 144) cell lines were analysed. The expression of Notch pathway elements was assessed by RT–PCR, real-time PCR (Notch 1), and by immunoblots (Notch 1 extracellular domain (EC), HES1). The proliferation and colony formation of A2780 cells were measured after stable transfection with activated Notch 1 (intracellular domain). Jagged 2, Delta-like-1, Manic Fringe, and TSL1 were expressed more frequently in adenocarcinomas whereas Deltex, Mastermind, and Radical Fringe were more frequent in adenomas. Quantitative PCR revealed decreased Notch 1 mRNA in ovarian adenocarcinomas compared with adenomas. The expression of Notch 1-EC protein was similar in benign and malignant tumours. HES1 protein was strongly expressed in 18/19 ovarian cancers and borderline tumours but not in adenomas. Transfecting A2780 cells with active Notch 1-IC resulted in a proliferative and colony formation advantage compared to mock transfected cells. Thus, Notch pathway elements are expressed in ovarian epithelial tumours and some of them are differentially expressed between adenomas and carcinomas. The Notch pathway could be a target for the development of therapies for ovarian cancer.