Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells

被引：64

作者：

Mitsuhashi, Yuko ^{[1
]}

Horiuchi, Akiko ^{[1
]}

Miyamoto, Tsutomu ^{[1
]}

Kashima, Hiroyasu ^{[1
]}

Suzuki, Akihisa ^{[1
]}

Shiozawa, Tanri ^{[1
]}

机构：

[1] Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Matsumoto, Nagano 3908621, Japan

来源：

HISTOPATHOLOGY | 2012年 / 60卷 / 05期

关键词：

endometrial carcinoma; immunohistochemistry; invasion; Notch; -secretase inhibitor; BREAST-CANCER; TUMOR ANGIOGENESIS; INHIBITS INVASION; DOWN-REGULATION; UP-REGULATION; GROWTH; EXPRESSION; ACTIVATION; APOPTOSIS; PATHWAY;

D O I：

10.1111/j.1365-2559.2011.04158.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：826 / 837

页数：12

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