EphB4 expression and biological significance in prostate cancer
EphB4 expression and biological significance in prostate cancer
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DOI：
10.1158/0008-5472.can-04-2667
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发表时间：
2005-06-01
期刊：
影响因子：
11.2
通讯作者：
Gill, PS
中科院分区：
文献类型：
--
作者：
Xia, GB;Kumar, SR;Gill, PS
前列腺癌是男性最常见的癌症。晚期前列腺癌扩散到腺体以外是无法治愈的。识别调节肿瘤扩散到区域结节和远处的因素将指导新的诊断、预后和治疗靶点的发展。本研究的目的是研究EphB4在前列腺癌中的表达及其生物学作用。在所评估的72例(89%)前列腺癌组织中，有EphB4mRNA的表达。EphB4蛋白在大多数(41/62，66%)肿瘤组织和3/20(15916)正常前列腺组织中表达。EphB4在良性前列腺上皮细胞系中几乎不表达或不表达，而在所有前列腺癌细胞系中均有不同程度的表达。在PC3前列腺癌细胞系中，EphB4蛋白水平很高，而在PC3转移克隆(PC3M)中，EphB4蛋白水平高出数倍，其中过度表达伴随着EphB4基因的扩增。EphB4的表达是由PTEN、P53的缺失诱导的，由表皮生长因子/表皮生长因子受体和胰岛素样生长因子-1/胰岛素样生长因子-IR诱导。使用EphB4短干扰RNA或反义寡核苷酸敲除EphB4蛋白可显著抑制前列腺癌细胞的生长/存活、迁移和侵袭，并诱导细胞凋亡。体内靶向EphB4的反义寡核苷酸在小鼠人肿瘤移植瘤模型中显示出抗肿瘤活性。这些数据显示了EphB4在前列腺癌中的作用，并为研究EphB4在诊断、预后和治疗方面的应用提供了理论基础。
Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15916) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-1/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.