Enhancer of Zeste Homolog 2 Expression Is Associated With Tumor Cell Proliferation and Invasion in Cervical Cancer

被引:30
作者
Fang, Jing [1 ]
Zhang, Mingxin [2 ]
Li, Qiling [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Obstet & Gynaecol, Affiliated Hosp 1, Xian 710061, Shaanxi Prov, Peoples R China
[2] Xi An Jiao Tong Univ, Dept Thorac Oncosurg, Affiliated Hosp 1, Xian 710061, Shaanxi Prov, Peoples R China
关键词
Enhancer of zeste homolog 2; Cervical cancer; Proliferation; Invasion; POLYCOMB GROUP GENE; POOR-PROGNOSIS; GASTRIC-CANCER; EZH2; AGGRESSIVENESS; CARCINOMA; LYMPHOMA; PROSTATE; BLADDER; BREAST;
D O I
10.1097/MAJ.0b013e31821335a9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Enhancer of zeste homolog 2 (EZH2) has been reported to be associated with biological malignancy in several cancers. High expression of EZH2 is associated with tumor cell proliferation, invasion and metastasis and has important clinicopathologic significance. However, little is known about the function and mechanisms of EZH2 in cervical cancer. Methods: This study was conducted to investigate the clinical value of EZH2 expression in cervical cancer and the association between EZH2 and possible downstream proteins using EZH2-targeted interfering RNA. Results: EZH2 expression rate was significantly greater in cervical cancer tissue than in normal cervical tissue both in mRNA and protein level. High EZH2 expression was significantly associated with differentiation, depth and lymphatic invasion. EZH2 gene RNAi resulted in inhibition of cell growth, cell cycle arrest and decreased ability of invasion in C33A cells. PCNA and MMP-2 expressions were downregulated, whereas p21 was upregulated after inhibition of EZH2. Conclusions: High EZH2 expression may be associated with tumor cell proliferation and invasion in cervical cancer, and that EZH2 may be one of the candidates for new molecular therapeutic targets for the treatment of cervical cancer.
引用
收藏
页码:198 / 204
页数:7
相关论文
共 20 条
[1]   p21 in cancer: intricate networks and multiple activities [J].
Abbas, Tarek ;
Dutta, Anindya .
NATURE REVIEWS CANCER, 2009, 9 (06) :400-414
[2]   EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast [J].
Bachmann, IM ;
Halvorsen, OJ ;
Collett, K ;
Stefansson, IM ;
Straume, O ;
Haukaas, SA ;
Salvesen, HB ;
Otte, AP ;
Akslen, LA .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (02) :268-273
[3]   EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].
Adrian P. Bracken ;
Diego Pasini ;
Maria Capra ;
Elena Prosperini ;
Elena Colli ;
Kristian Helin .
The EMBO Journal, 2003, 22 (20) :5323-5335
[4]   Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis [J].
Breuer, RHJ ;
Snijders, PJF ;
Smit, EF ;
Sutedja, TG ;
Sewalt, RGAB ;
Otte, AP ;
van Kemenade, FJ ;
Postmus, PE ;
Meijer, CJLM ;
Raaphorst, FM .
NEOPLASIA, 2004, 6 (06) :736-743
[5]   Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer [J].
Choi, Jung Hye ;
Song, Young Soo ;
Yoon, Jin Sun ;
Song, Kang Won ;
Lee, Young Yiul .
APMIS, 2010, 118 (03) :196-202
[6]   High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy [J].
He, Li-Ru ;
Liu, Meng-Zhong ;
Li, Bin-Kui ;
Jia, Wei-Hua ;
Zhang, Ying ;
Liao, Yi-Ji ;
Chen, Yang-Chao ;
Zhang, Lan-Jun ;
Guan, Xin-Yuan ;
Zeng, Yi-Xin ;
Kung, Hsiang-Fu ;
Xie, Dan .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (01) :138-147
[7]   Activation of the Enhancer of Zeste Homologue 2 Gene by the Human Papillomavirus E7 Oncoprotein [J].
Holland, Daniela ;
Hoppe-Seyler, Karin ;
Schuller, Bettina ;
Lohrey, Claudia ;
Maroldt, Julia ;
Duerst, Matthias ;
Hoppe-Seyler, Felix .
CANCER RESEARCH, 2008, 68 (23) :9964-9972
[8]   EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells [J].
Kleer, CG ;
Cao, Q ;
Varambally, S ;
Shen, RL ;
Ota, L ;
Tomlins, SA ;
Ghosh, D ;
Sewalt, RGAB ;
Otte, AP ;
Hayes, DF ;
Sabel, MS ;
Livant, D ;
Weiss, SJ ;
Rubin, MA ;
Chinnaiyan, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11606-11611
[9]   Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer [J].
Matsukawa, Yasuko ;
Semba, Shuho ;
Kato, Hirotaka ;
Ito, Akihiko ;
Yanagihara, Kazuyoshi ;
Yokozaki, Hiroshi .
CANCER SCIENCE, 2006, 97 (06) :484-491
[10]   Connections between epigenetic gene silencing and human disease [J].
Moss, Timothy J. ;
Wallrath, Lori L. .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2007, 618 (1-2) :163-174