title: Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells.
abstract: OBJECTIVE
  The aim of this study was to investigate the significance of the expression of Notch-related molecules in endometrial carcinoma.
  
  
  RESULTS
  The expression of Notch receptors (Notch1 and 3) and Notch ligands [Jagged (JAG) 1 and Delta-like (DLL) 4] was examined immunohistochemically in 37 normal and 76 malignant endometrial tissue samples. For each section, immunohistochemical staining was scored using a positivity index (PI, full score; 200). The effects of a Notch inhibitor, DAPT, on cell proliferation, invasion and motility were investigated using endometrial carcinoma cell lines. The PIs for Notch1 (mean±SD 90.4±15.3), Notch3 (95.6 ± 20.4), JAG1 (95.5±10.0) and DLL4 (88.2±9.6), were significantly higher in endometrial carcinoma than normal endometrium. The PI for Notch1 was associated significantly with advanced International Federation of Gynecologists & Obstetricians (FIGO) stage. In addition, patients with tumours showing high expression of both Notch1 and JAG1 had a poor prognosis compared with those having double-negative carcinomas (P=0.015). DAPT suppressed invasiveness of cells derived from the endometrial carcinoma cell line KLE.
  
  
  CONCLUSIONS
  The Notch1-JAG1 axis may enhance the invasive properties of endometrial carcinomas, which suggests the Notch pathway may be a promising target for the treatment of this malignancy.
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mitsuhashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kashima
authors.forename: Akihisa
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D051881:Receptor, Notch1 / Q000378:metabolism*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D004151:Dipeptides; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; C499374:NOTCH3 protein, human; D051881:Receptor, Notch1; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins