The Notch pathway in ovarian carcinomas and adenomas.
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.
Hopfer
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Department of Clinical Research, University of Bern, Bern, Switzerland.
Zwahlen
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Fey
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Aebi
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D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins; D049109:Cell Proliferation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human