Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder
Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder
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DOI：
10.1158/1078-0432.ccr-05-1047
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发表时间：
2005-12-15
影响因子：
11.5
通讯作者：
Gudas, LJ
中科院分区：
文献类型：
--
作者：
Raman, JD;Mongan, NP;Gudas, LJ
目的：Polycomb group基因EZH 2是一个转录抑制因子，参与基因沉默。EZH 2的扩增已经在几种恶性肿瘤中报道，包括前列腺、乳腺和淋巴瘤。我们评估了患者膀胱标本中EZH 2 mRNA和蛋白的表达以及5种膀胱癌细胞系中EZH 2 mRNA的表达。实验设计：通过逆转录- PCR（RT-PCR）评估38例膀胱组织标本中EZH 2 mRNA的表达。我们还使用亲和纯化的人EZH 2抗体，使用免疫组织化学方法评估了39例膀胱癌标本的EZH 2蛋白表达。结果：14例膀胱癌组织中EZH 2 mRNA表达阳性率为36%（5/14），膀胱肿瘤组织中EZH 2 mRNA表达阳性率为88%（21/24），两者差异有统计学意义（P = 0.003）。所有浸润性肿瘤（10/10）都有可检测到的EZH 2 mRNA表达，而14例浅表性肿瘤中有11例（79%）有EZH 2 mRNA表达。此外，在100%（16/16）的高级别膀胱肿瘤中观察到EZH 2 mRNA表达，而在50%（4/8）的低级别肿瘤中观察到EZH 2 mRNA表达（P = 0.01）。同时，EZH 2蛋白在肿瘤组织中的表达高于非肿瘤组织（78%比69%，P < 0.005）。浅表性和浸润性肿瘤之间EZH 2蛋白水平无差异。与正常尿路上皮相比，高级别肿瘤的EZH 2染色增加（78%对68%，P < 0.005），而低级别病变则没有。四个人膀胱癌细胞系表达高水平的EZH 2，而只有低水平的检测在一个细胞line.Conclusions：我们报告了一个显着增加EZH 2在膀胱移行细胞癌的表达与正常尿路上皮相比。这些数据表明，与其他人类恶性肿瘤相似，EZH 2表达增加与膀胱肿瘤发生相关。
Purpose:The Polycomb group gene, EZH2, functions as a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies, including prostate, breast, and lymphoma. We evaluated EZH2 mRNA and protein expression in bladder specimens from patients and the EZH2 mRNA expression in five bladder cancer cell lines.Experimental Design: EZH2 mRNA expression was assessed by reverse transcription- PCR (RT-PCR) in 38 bladder tissue specimens. We also evaluated 39 bladder cancer specimens for EZH2 protein expression using immunohistochemistry with affinity-purified antibodies to human EZH2. In addition, five human bladder cancer cell lines were analyzed by RT-PCR for EZH2 mRNA expression.Results: Five of 14 (36%) nonturnor bladder specimens versus 21 of 24 (88%) bladder tumors showed EZH2 mRNA expression (P = 0,003). All of the invasive tumors (10 of 10) had detectable EZH2 mRNA expression, compared with 11 of 14 (79%) superficial tumors. In addition, EZH2 mRNA expression was noted in 100% (16 of 16) of high-grade bladder tumors versus 50% (4 of 8) of low-grade tumors (P = 0.01). EZH2 protein expression, meanwhile, was increased in neoplastic tissue compared with nonturnor urothelium (78% versus 69% of nuclei, P < 0.005). There were no differences in EZH2 protein levels between superficial and invasive tumors. High-grade tumors had increased EZH2 staining compared with normal urothelium (78% versus 68%, P < 0.005), whereas low-grade lesions did not. Four of five human bladder cancer cell lines expressed high levels of EZH2, whereas only low levels were detected in one cell line.Conclusions: We report a significant increase in EZH 2 expression in transitional cell carcinoma of the bladder compared with normal urothelium. These data suggest that similar to other human malignancies, increased EZH2 expression correlates with oncogenesis of the bladder.