ETS基因重排在前列腺癌中的特征分析

山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (06): 94-99.

ETS基因重排在前列腺癌中的特征分析

戚美1，杨晓庆1，王林1,2，张娟3，王妍3，韩博1,3

1.山东大学医学院病理学教研室, 济南 250012； 2.山东省医学科学院，济南 250012；
3.山东大学齐鲁医院病理科, 济南 250012

收稿日期:2013-03-10 出版日期:2013-06-10 发布日期:2013-06-10
通讯作者: 韩博，E-mail: boh@sdu.edu.cn
基金资助:
国家自然科学基金面上项目 (81072110)；山东大学自主创新基金项目(2010TB012)；教育部留学回国人员科研启动基金。

Characteristic analysis of ETS gene rearrangement in prostate cancer

QI Mei1， YANG Xiao-qing1， WANG Lin1,2， ZHANG Juan3, WANG Yan3， HAN Bo1,3

1. Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China；
2. Shandong Academy of Medical Sciences, Jinan 250012, China；
3. Department of Pathology, Qilu Hospital of Shandong University, Jinan 250012, China

Received:2013-03-10 Online:2013-06-10 Published:2013-06-10

摘要/Abstract

摘要：

目的确定前列腺癌人群中ETS家族常见成员基因ERG、ETV1、ETV4和ETV5重排的发生频度；分析ERG基因重排与常见临床及分子病理学指标的关联；验证ERG过表达是否促进前列腺癌细胞上皮间质转化(EMT)。方法荧光原位杂交技术(FISH)检测128例前列腺癌患者肿瘤组织中ERG、ETV1、ETV4和ETV5基因的重排和PTEN基因的缺失；免疫组织化学PV-9000二步法检测前列腺癌组织中雄激素受体(AR) 及转录因子SOX4的表达；采用siRNA、Real-time PCR和Western blot检测ERG与前列腺癌细胞EMT的关联。结果 ERG在前列腺癌人群中重排发生率为23% (25/108)，其中60%(15/25)的ERG重排患者伴有ERG 5’ 端的缺失。ETV1、ETV4和ETV5的重排发生率分别为2% (2/109)、 1%(1/103)和0%。ERG基因重排与肿瘤远处转移呈正相关(P<0.05)，但与Gleason 评分、术前PSA水平及肿瘤临床分期等无关联。ERG基因重排与PTEN基因的缺失、SOX4蛋白的表达均呈正相关(P<0.05)，但与AR的表达未见相关性；体外实验显示，干扰ERG的表达可抑制前列腺癌Vcap细胞EMT的发生。结论 ERG基因重排在我国前列腺癌患者中的发生频率较西方国家低。ERG基因重排与EMT相关，并可能与其他基因协同发挥促癌作用。

关键词: 基因，ETS；基因，ERG；基因重排；前列腺肿瘤；上皮间质转化

Abstract:

Objective To determine the frequency of ETS (ERG, ETV1, ETV4 and ETV5) gene rearrangement, analyze the relationship between ERG rearrangement and prove whether ERG overexpression can promote the epitheial-mesenchymal transition (EMT) process. Methods Fluorescence in situ hybridization (FISH) was performed to validate the ETS gene aberrations and PTEN deletions of 128 PCa patients. Expression of androgen receptor (AR) and SOX4 was evaluated by using PV-9000 two-step immunohistochemistry method. SiRNA、Real-time PCR and western blot were utilized to study the link between ERG aberration and EMT in PCa in vitro. Results Overall，ERG rearrangement was present in 23% (25/108) cases, of which 60% (15/25) showed deletion of the 5’end of ERG. Rearrangement of ETV1，ETV4 and ETV5 occurred in 2% (2/109), 1%(1/103) and 0% cases, respectively. ERG rearrangement was positively associated with tumor distant metastasis (P<0.05), but not with Gleason score, preoperative PSA values and clinical tumor staging. Significant positive correlations were noted between ERG rearrangement and PTEN deletion as well as SOX4 protein overexpression (P<0.05), but not with AR expression. In vitro study revealed that ERG silencing could inhibit EMT in Vcap cells. Conculsion The freqneucy of ERG rearrangement is significantly lower in China than that in western countries. ERG rearrangement is associated with EMT, and may cooperate with other genes to promote cancer development.

Key words: Genes, ETS； Genes, ERG； Gene rearrangement； Prostatic neoplasia； Epitheialmesenchymal transition

中图分类号:

R966

戚美1，杨晓庆1，王林1,2，张娟3，王妍3，韩博1,3. ETS基因重排在前列腺癌中的特征分析[J]. 山东大学学报(医学版), 2013, 51(06): 94-99.

QI Mei1， YANG Xiao-qing1， WANG Lin1,2， ZHANG Juan3, WANG Yan3， HAN Bo1,3. Characteristic analysis of ETS gene rearrangement in prostate cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(06): 94-99.

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