Expression of Ephb2 and Ephb4 in breast carcinoma
Expression of Ephb2 and Ephb4 in breast carcinoma
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DOI：
10.1007/bf02893405
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Nesland, JM
中科院分区：
文献类型：
--
作者：
Wu, QH;Suo, ZH;Nesland, JM
Eph受体酪氨酸激酶及其细胞表面结合配体肝配蛋白在多种生物过程中发挥关键作用。Eph受体包括最大的受体酪氨酸激酶家族，其由八种EphA受体（具有五种相应的肝配蛋白A配体）和六种EphB受体（具有三种相应的跨膜肝配蛋白B配体）组成。EphB受体和ephrinB配体最初被鉴定为神经元寻路分子，后来被证明是血管发生和胚胎发生的关键调节因子。越来越多的研究表明Eph受体参与血管生成和肿瘤发生。本研究旨在探讨EphB 2和EphB 4在乳腺癌中的表达。半定量RT-PCR和免疫组化检测EphB 2和EphB 4的表达模式。对94例乳腺癌、9例正常乳腺组织和4株乳腺癌细胞系的临床病理和生存相关性进行统计学分析。EphB 2蛋白阴性表达1例（1%），弱表达16例（17%），中表达29例（31%），强表达48例（51%）。EphB 4阴性表达6例（6%），弱表达27例（29%），中表达28例（30%），强表达33例（35%）。EphB 2和EphB 4的RTPCR产物在所有标本中均可检测到。EphB 2蛋白表达增加与总生存率呈负相关，并且有一种趋势，即EphB 2蛋白表达增加与较短的无病生存期相关，而EphB 4蛋白表达与组织学分级和分期相关。EphB 4膜染色随S期分数增加而增加，并与DNA非整倍体有关。这些发现表明EphB 2和EphB 4都参与了乳腺癌的发展，这两种分子都可能是潜在的预测标志物。
Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, play key roles in diverse biological processes. Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors ( with five corresponding ephrinA ligands) and six EphB receptors ( with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, EphB receptors and ephrinB ligands are later proved to be crucial regulators of vasculogenesis and embryogenesis. More studies indicate that Eph receptors are involved in angiogenesis and tumorigenesis. This study aimed to investigate the expression of EphB2 and EphB4 in breast carcinomas. Semiquantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of EphB2 and EphB4. Clinicopathological and survival correlations were statistically analyzed in a series of 94 breast carcinomas, 9 normal specimens and 4 breast carcinoma cell lines. 1(1%), 16(17%), 29(31%), 48(51%) of the 94 tumors were negative, weak, moderate and strong EphB2 protein expression, respectively. 6(6%), 27(29%), 28(30%), 33(35%) of the tumors were negative, weak, moderate and strong EphB4 expression, respectively. Both EphB2 and EphB4 RTPCR products could be detected in all specimens. Increased EphB2 protein expression was negatively associated with overall survival, and there was a trend that increased EphB2 protein expression was correlated with shorter disease free survival, while EphB4 protein expression was associated with histological grade and stage. EphB4 membrane staining was increased with S phase fraction and associated with DNA aneuploidy. These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers.