Hec1/Ndc80 is overexpressed in human gastric cancer and regulates cell growth

被引：57

作者：

Qu, Ying ^{[1
]}

Li, Jianfang ^{[1
]}

Cai, Qu ^{[1
]}

Liu, Bingya ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Key Lab Gastr Neoplasms, Shanghai Inst Digest Surg, Dept Surg,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China

来源：

JOURNAL OF GASTROENTEROLOGY | 2014年 / 49卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Hec1; Gastric cancer; Cell cycle; Apoptosis; GENE-EXPRESSION; DNA-PLOIDY; HEPATOCELLULAR-CARCINOMA; SPINDLE CHECKPOINT; MITOTIC CHECKPOINT; COPY NUMBER; KINETOCHORE; ANEUPLOIDY; SIGNATURE; PROTEIN;

D O I：

10.1007/s00535-013-0809-y

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Chromosomal instability caused by abnormal cell division is a major cause of heterogeneity which evokes highly complex and malignant features of gastric cancer. Hec1/Ndc80 is critical in regulating proper cell division at the G2/M phase. The aim of our study is to investigate the in vitro and in vivo effects of Hec1 on gastric cancer cell growth. The mRNA levels of Hec1 in human normal and cancer tissues were analyzed using the Oncomine database. Hec1 mRNA and protein levels in human gastric cancer tissues were analyzed by quantitative realtime-PCR and immunohistochemical staining, respectively. The effects of Hec1 on cell growth were explored by Hec1 knockdown and Hec1 overexpression. Apoptosis and cell cycle distributions were analyzed by flow cytometry. In vivo tumorigenicity was performed by engrafting tumor cells into nude mice. Hec1 mRNA and protein were broadly overexpressed in many human cancers including gastric cancer. Hec1 knockdown dramatically suppressed gastric cancer cell growth in vitro and in vivo, induced apoptosis, and arrested cell division at the G2/M phase. On the contrary, Hec1 overexpression moderately promoted gastric cancer cell growth in vivo. Hec1 overexpression induced asymmetrical chromosome alignments, abnormal cell division, and thus rendered chromosomal instability. Hec1 is critical in maintaining the in vitro and in vivo growth of gastric cancer cells. Elevated Hec1 levels may occur at the early stage of gastric tumorigenesis.

引用

页码：408 / 418

页数：11

共 51 条

[1]

Badea L, 2008, HEPATO-GASTROENTEROL, V55, P2016

[2] A Dominantly Acting Murine Allele of Mcm4 Causes Chromosomal Abnormalities and Promotes Tumorigenesis [J].

Bagley, Bruce N. ;

Keane, Thomas M. ;

Maklakova, Vilena I. ;

Marshall, Jonathon G. ;

Lester, Rachael A. ;

Cancel, Michelle M. ;

Paulsen, Alex R. ;

Bendzick, Laura E. ;

Been, Raha A. ;

Kogan, Scott C. ;

Cormier, Robert T. ;

Kendziorski, Christina ;

Adams, David J. ;

Collier, Lara S. .

PLOS GENETICS, 2012, 8 (11)

[3] The spindle checkpoint, aneuploidy, and cancer [J].

Bharadwaj, R ;

Yu, HT .

ONCOGENE, 2004, 23 (11) :2016-2027

[4] Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy [J].

Bieche, Ivan ;

Vacher, Sophie ;

Lallemand, Francois ;

Tozlu-Kara, Senguel ;

Bennani, Hind ;

Beuzelin, Michele ;

Driouch, Keltouma ;

Rouleau, Etienne ;

Lerebours, Florence ;

Ripoche, Hugues ;

Cizeron-Clairac, Geraldine ;

Spyratos, Frederique ;

Lidereau, Rosette .

MOLECULAR CANCER, 2011, 10

[5] Gene expression in early stage cervical cancer [J].

Biewenga, Petra ;

Buist, Marrije R. ;

Moerland, Perry D. ;

van Thernaat, Emiel Ver Loren ;

van Kampen, Antoine H. C. ;

ten Kate, Fiebo J. W. ;

Baas, Frank .

GYNECOLOGIC ONCOLOGY, 2008, 108 (03) :520-526

[6] Molecular architecture of the kinetochore-microtubule interface [J].

Cheeseman, Iain M. ;

Desai, Arshad .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (01) :33-46

[7] The conserved KMN network constitutes the core microtubule-binding site of the kinetochore [J].

Cheeseman, Iain M. ;

Chappie, Joshua S. ;

Wilson-Kubalek, Elizabeth M. ;

Desai, Arshad .

CELL, 2006, 127 (05) :983-997

[8] HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis [J].

Chen, YM ;

Riley, DJ ;

Chen, PL ;

Lee, WH .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (10) :6049-6056

[9] Gene Expression Signature-Based Prognostic Risk Score in Gastric Cancer [J].

Cho, Jae Yong ;

Lim, Jae Yun ;

Cheong, Jae Ho ;

Park, Yun-Yong ;

Yoon, Se-Lyun ;

Kim, Soo Mi ;

Kim, Sang-Bae ;

Kim, Hoguen ;

Hong, Soon Won ;

Park, Young Nyun ;

Noh, Sung Hoon ;

Park, Eun Sung ;

Chu, In-Sun ;

Hong, Waun Ki ;

Ajani, Jaffer A. ;

Lee, Ju-Seog .

CLINICAL CANCER RESEARCH, 2011, 17 (07) :1850-1857

[10] Genome-wide expression profile of sporadic gastric cancers with microsatellite instability [J].

D'Errico, Mariarosaria ;

de Rinaldis, Emanuele ;

Blasi, Monica F. ;

Viti, Valentina ;

Falchetti, Mario ;

Calcagnile, Angelo ;

Sera, Francesco ;

Saieua, Calogero ;

Ottini, Laura ;

Palli, Domenico ;

Palombo, Fabio ;

Giuliani, Alessandro ;

Dogliotti, Eugenia .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (03) :461-469

← 1 2 3 4 5 6 →