RRC ID 39049
Author Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T.
Title Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells.
Journal Histopathology
Abstract AIMS:The aim of this study was to investigate the significance of the expression of Notch-related molecules in endometrial carcinoma.
METHODS AND 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.
Volume 60(5)
Pages 826-37
Published 2012-4-1
DOI 10.1111/j.1365-2559.2011.04158.x
PMID 22348356
MeSH Adaptor Proteins, Signal Transducing Biomarkers, Tumor / metabolism Calcium-Binding Proteins / metabolism* Carcinoma, Endometrioid / drug therapy Carcinoma, Endometrioid / metabolism* Cell Adhesion / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Dipeptides / pharmacology Endometrial Neoplasms / drug therapy Endometrial Neoplasms / metabolism* Female Humans Intercellular Signaling Peptides and Proteins / metabolism* Jagged-1 Protein Membrane Proteins / metabolism* Neoplasm Invasiveness Prognosis Receptor, Notch1 / metabolism* Receptor, Notch3 Receptors, Notch / metabolism* Serrate-Jagged Proteins
IF 3.626
Times Cited 42
WOS Category PATHOLOGY CELL BIOLOGY
Resource
Human and Animal Cells HHUA(RCB0658)