Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features
Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features
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DOI：
10.1002/ijc.23890
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发表时间：
2009-01-01
影响因子：
6.4
通讯作者：
Yes, Chuanzhong
中科院分区：
文献类型：
--
作者：
Guan, Ming;Xu, Chong;Yes, Chuanzhong
EphA 7是Eph/ephrins家族的成员，在肿瘤发生中发挥着多种作用。我们研究的目的是研究前列腺癌中EphA 7的功能和结构改变，并确定这些发现是否与前列腺癌的临床病理特征相关。应用定量RT-PCR、甲基化特异性PCR和免疫组化方法检测了48例前列腺癌、31例前列腺增生、5例正常前列腺组织和3株前列腺细胞系（LNCaP、DU 145和PC-3）的甲基化水平。48例前列腺癌中有23例（47.9%）和31例增生中有2例（6.5%）检测到EphA 7 mRNA表达下调或缺失。EphA 7启动子区的甲基化分别存在于48例癌中的20例（41.7%）和31例增生中的6例（19.3%）。免疫组化结果显示，30例癌组织中有10例（33.3%）EphA 7蛋白表达缺失，其中8例（80.0%）存在甲基化。EphA 7甲基化的频率在具有较高Gleason评分的癌症患者中较高。用5-氮杂-2 '-脱氧胞苷处理具有甲基化的DU 145细胞重新激活EphA 7的表达。EphA 7在DU 145细胞中的异位表达不抑制细胞生长，但抑制集落形成。我们的研究提供了EphA 7表观遗传失活可能参与前列腺癌发生的证据。(C)2008 Wiley-Liss，Inc.
EphA7 is a member of Eph/ephrins family and play diverse roles in carcinogenesis. The aim of our study was to investigate functional and structural alterations of EphA7 in prostate cancer and determine if those findings correlate with the clinicopathologic features of prostate cancer. Forty-eight prostate carcinomas, 31 benign prostate hyperplasias, 5 normal prostate tissues and 3 prostate cell lines (LNCaP, DU145 and PC-3) were examined with quantitative RT-PCR, methylation-specific PCR and immunohistochemistry. Downregulation or loss of EphA7 mRNA expression was detected in 23 of 48 (47.9%) prostate carcinomas, and 2 of 31 (6.5%) hyperplasias. Methylation of the EphA7 promoter region was present in 20 of 48 (41.7%) of carcinomas and 6 of 31 (19.3%) hyperplasias, respectively. Immunostaining analysis showed EphA7 protein was absent in 10 of 30 (33.3%) carcinoma samples available and 8 of them (80.0%) exhibited hypermethylation. The frequency of EphA7 methylation was higher in cancer patients with higher Gleason score. Treatment of DU145 cells harboring methylation with 5-aza-2'-deoxycytidine reactivated expression of EphA7. Ectopic expression of EphA7 in DU145 cells did not suppress cell growth but inhibited colony formation. Our study provides evidence that epigenetic inactivation of EphA7 may be involved in prostate carcinogenesis. (C) 2008 Wiley-Liss, Inc.