n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester and Carcinoma--Endometrioid

The aim of this study was to investigate the significance of the expression of Notch-related molecules in endometrial carcinoma.. 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.. 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.

Topics: Adaptor Proteins, Signal Transducing; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma, Endometrioid; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dipeptides; Endometrial Neoplasms; Female; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Membrane Proteins; Neoplasm Invasiveness; Prognosis; Receptor, Notch1; Receptor, Notch3; Receptors, Notch; Serrate-Jagged Proteins