Loss of DMBT1 Expression in Human Prostate Cancer and Its Correlation with Clinical Progressive Features
Loss of DMBT1 Expression in Human Prostate Cancer and Its Correlation with Clinical Progressive Features
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人前列腺癌中 DMBT1 表达的缺失及其与临床进展特征的相关性
DOI：
10.1016/j.urology.2010.09.023
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发表时间：
2011-02-01
期刊：
影响因子：
2.1
通讯作者：
Jiang, Haowen
中科院分区：
文献类型：
--
作者：
Du, Junhua;Guan, Ming;Jiang, Haowen
目的研究前列腺癌组织中DMBT 1基因的改变，并探讨其与前列腺癌临床病理特征的相关性。方法应用基因芯片和实时荧光定量PCR技术，分析DNA甲基转移酶抑制剂对前列腺癌细胞系LNCaP和PC-3中DMBT 1表达的影响。结果5-aza-2 '-deoxycytidine处理后，PC 3细胞中DMBT 1的表达恢复，而LNCaP细胞中DMBT 1的表达无明显改变。在前列腺癌中观察到DMBT 1 mRNA和蛋白表达的下调或缺失，但在良性组织中未观察到。免疫组化结果显示，14例Gleason评分为8-10分的前列腺癌组织中DMBT 1蛋白表达缺失，16例Gleason评分为4-7分的前列腺癌组织中DMBT 1蛋白表达较弱，15例良性前列腺组织中DMBT 1蛋白表达较强。DMBT 1表达缺失与局部浸润（P = .048）和骨转移（P = .039）相关，但与患者年龄、前列腺特异性抗原水平或诊断时的肿瘤分级无关。结论：我们的研究提供了DMBT 1表达缺失与前列腺癌相关的证据，表明DMBT 1可能在前列腺癌发生中起抑癌基因的作用。泌尿学77：509.e9-509.e13，2011年。(C)2011 Elsevier Inc.
OBJECTIVES To investigate alterations of DMBT1 in prostate cancer and determine the correlation of its alterations to the clinicopathologic features of prostate cancer. DMBT1 has been proposed as a candidate tumor suppressor gene for epithelial cancer.METHODS The alterations of DMBT1 expression after treatment with DNA methyltransferase inhibitor in 2 prostate cancer cell lines (LNCaP and PC-3) were analyzed by genome microarray and real-time polymerase chain reaction (PCR). A total of 36 prostate cancer tissues and 16 benign prostatic tissues were evaluated with reverse transcription-PCR, Western blot, and immunohistochemistry for DMBT1 expression.RESULTS Treatment with 5-aza-2'-deoxycytidine reactivated expression of DMBT1 in PC3 cells, but not in LNCaP cells. Downregulation or loss of DMBT1 mRNA and protein expression was observed in prostate cancer, but not in benign tissues. Immunostaining analysis showed DMBT1 protein was absent in 14 cancer samples with Gleason score of 8-10 and weakly stained in 16 cancer samples with Gleason score of 4-7, compared with strong immunostaining in all 15 benign prostatic tissues. Loss of DMBT1 expression was correlated with local invasion (P = .048) and bone metastasis (P = .039) but was not correlated with patient age, prostate-specific antigen level, or tumor grade at diagnosis.CONCLUSIONS Our study provides evidence that loss of DMBT1 expression is associated with prostate cancer, suggesting that DMBT1 may function as a tumor suppressor gene in prostate carcinogenesis. UROLOGY 77: 509.e9-509.e13, 2011. (C) 2011 Elsevier Inc.