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.
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收藏
页码：826 / 837
页数：12
相关论文
共 43 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]  
ALBINI A, 1987, CANCER RES, V47, P3239
[3]   Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].
Bapat, SA ;
Mali, AM ;
Koppikar, CB ;
Kurrey, NK .
CANCER RESEARCH, 2005, 65 (08) :3025-3029
[4]   Targeted Knockdown of Notch1 Inhibits Invasion of Human Prostate Cancer Cells Concomitant with Inhibition of Matrix Metalloproteinase-9 and Urokinase Plasminogen Activator [J].
Bin Hafeez, Bilal ;
Adhami, Vaqar Mustafa ;
Asim, Mohammad ;
Siddiqui, Imtiaz A. ;
Bhat, Kumar M. ;
Zhong, Weixiong ;
Saleem, Mohammad ;
Din, Maria ;
Setaluri, Vijayasaradhi ;
Mukhtar, Hasan .
CLINICAL CANCER RESEARCH, 2009, 15 (02) :452-459
[5]   The pattern of expression of Notch protein members in normal and pathological endometrium [J].
Cobellis, Luigi ;
Caprio, Francesca ;
Trabucco, Elisabetta ;
Mastrogiacomo, Annunziata ;
Coppola, Gabriele ;
Manente, Lucrezia ;
Colacurci, Nicola ;
De Falco, Maria ;
De Luca, Antonio .
JOURNAL OF ANATOMY, 2008, 213 (04) :464-472
[6]   Meningioma transcript profiles reveal deregulated notch signaling pathway [J].
Cuevas, IC ;
Slocum, AL ;
Jun, P ;
Costello, JF ;
Bollen, AW ;
Riggins, GJ ;
McDermott, MW ;
Lal, A .
CANCER RESEARCH, 2005, 65 (12) :5070-5075
[7]   Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway [J].
Dong, Peixin ;
Xu, Zhujie ;
Jia, Nan ;
Li, Dajin ;
Feng, Youji .
MOLECULAR CANCER, 2009, 8
[8]   Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells [J].
Fakhry, Hussein ;
Miyamoto, Tsutomu ;
Kashima, Hiroyasu ;
Suzuki, Akihisa ;
Ke, He ;
Konishi, Ikuo ;
Shiozawa, Tanri .
HUMAN PATHOLOGY, 2010, 41 (06) :848-858
[9]   NOTCH Pathway Blockade Depletes CD133-Positive Glioblastoma Cells and Inhibits Growth of Tumor Neurospheres and Xenografts [J].
Fan, Xing ;
Khaki, Leila ;
Zhu, Thant S. ;
Soules, Mary E. ;
Talsma, Caroline E. ;
Gul, Naheed ;
Koh, Cheryl ;
Zhang, Jiangyang ;
Li, Yue-Ming ;
Maciaczyk, Jarek ;
Nikkhah, Guido ;
DiMeco, Francesco ;
Piccirillo, Sara ;
Vescovi, Angelo L. ;
Eberhart, Charles G. .
STEM CELLS, 2010, 28 (01) :5-16
[10]   Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine [J].
Fre, Silvia ;
Pallavi, S. K. ;
Huyghe, Mathilde ;
Lae, Marick ;
Janssen, Klaus-Peter ;
Robine, Sylvie ;
Artavanis-Tsakonas, Spyros ;
Louvard, Daniel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (15) :6309-6314
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