癌变·畸变·突变

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E2F5和MYC癌基因在前列腺癌中的表达及其意义

 阳1,周 亮2,陈佳鸿2,何慧婵2,钟惟德2,*   

  1. 1. 广州医科大学附属广州市第一人民医院心内科,广东 广州 510180;2. 广州医科大学附属广州市第一人民医院,广东省临床分子医学及分子诊断重点实验室,广东 广州 510180
  • 收稿日期:2013-05-07 修回日期:2013-06-18 出版日期:2013-07-30 发布日期:2013-07-30
  • 通讯作者: 钟惟德,E-mail:wdezhong@21cn.com
  • 作者简介:杨 阳 (1979- ),女,主管技师,硕士研究生,研究方向:临床病理。E-mail:103834338@qq.com
  • 基金资助:

    国家自然科学基金项目 (81170699),广州市卫生局重点项目 (201102A212015)

Expressions and significance of E2F5 and MYC oncogenes in prostate cancer

YANG Yang1ZHOU Liang2,CHEN Jia-hong2,HE Hui-chan2,ZHONG Wei-de2,*   

  1. 1. Department of Cardiology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180; 2. Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China
  • Received:2013-05-07 Revised:2013-06-18 Online:2013-07-30 Published:2013-07-30
  • Contact: ZHONG Wei-de,E-mail:wdezhong@21cn.com

摘要:

目的: 检测染色体8q21~24区域E2F5和MYC癌基因在前列腺癌 (prostate cancer,PCa) 细胞系、癌组织及癌旁组织中的表达,分析其表达水平与临床病理参数的关系,并探讨其意义。方法:采用DNA qPCR检测PCa细胞系Du145、LNCap、PC3和PCa组织标本中E2F5和MYC基因DNA拷贝数,Western blot和免疫组织化学技术检测前列腺癌和癌旁组织中E2F5和MYC蛋白的表达,结合患者临床病理参数进一步验证和分析蛋白表达及其临床意义。结果:DNA qPCR结果显示,PCa组织中E2F5和MYC DNA拷贝数较癌旁组织明显增加 (P<0.05或P<0.01),但在癌细胞系中其表达与对照组比较无明显变化 (P>0.05)。Western blot显示,在PCa组织中E2F5和MYC蛋白表达水平显著高于癌旁组织 (P<0.05或P<0.01)。免疫组化染色发现,与癌旁良性组织相比,E2F5和MYC蛋白表达显著增加 (P均<0.01)。而且,E2F5的过表达与高的Gleason评分 (P<0.01)、临床分期 (P=0.01)、阳性转移 (P <0.01)、生化复发阳性 (P<0.01)相关。MYC的过表达与阳性转移 (P=0.02)、生化复发阳性 (P=0.02)相关。且PCa组织中E2F5和MYC蛋白表达两者呈正相关关系 (rs=0.5,P<0.01)。结论:E2F5和MYC的表达增加可能与PCa的发生发展密切相关,E2F5可能是PCa新的潜在候选分子标志物。

关键词: 前列腺癌, E2F5, MYC, 实时荧光定量聚合酶链反应, 免疫组化, Western blot

Abstract:

OBJECTIVE: The aim of this study was to identify the expressions of E2F5 and MYC gene located in chromosomal region 8q21–24 in prostate cancer (PCa),adjacent benign prostate tissues and PCa cell lines,to analyze their expression levels and to explore theirs significances in PCa. METHODS:DNA qPCR analysis was carried out to evaluate the copy number changes of E2F5 and MYC genes in PCa tissues and PCa cell lines. Western blot and immunohistochemical staining were used to assess expressions of E2F5 and MYC in PCa and BPH tissues,and analyzed together with clinical pathological parameters. RESULTS:DNA qPCR revealed a significant copy number gain of E2F5 and MYC in PCa tissues but not in PCa cell lines (P<0.05 or P<0.01). In addition,Western blot analysis and immunohistochemical staining both found the significantly higher expression of E2F5 and MYC proteins in PCa tissues than those in adjacent benign specimens (all P<0.01). Moreover,the overexpression of E2F5 protein was significantly associated with a high Gleason score (P<0.01),an advanced clinical stage (P=0.01),a positive metastasis (P<0.01) and biochemical recurrence (P<0.01). The overexpression of MYC was more frequently found in PCa tissues with positive metastasis (P=0.02) and biochemical recurrence (P=0.02). Interestingly,there was a close correlation in the expression level of MYC in PCa tissues with that of E2F5 (rs=0.5,P<0.01). CONCLUSION:Overexpressions of E2F5 and MYC may play an important role in the development and progression of PCa. E2F5 may be a novel potential candidate marker for malignant PCa.

Key words: prostate cancer, E2F5, MYC, qPCR, imunohistochemistry, Western blot