Reference - Detail
RRC ID | 39049 |
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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) |