The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome.
The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome.
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受体酪氨酸激酶EPHB4在卵巢癌中过表达，提供生存信号并预测结果不佳。
DOI：
10.1038/sj.bjc.6603642
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发表时间：
2007-04-10
影响因子：
8.8
通讯作者：
Gill, P. S.
中科院分区：
文献类型：
--
作者：
Kumar, S. R.;Masood, R.;Spannuth, W. A.;Singh, J.;Scehnet, J.;Kleiber, G.;Jennings, N.;Deavers, M.;Krasnoperov, V.;Dubeau, L.;Weaver, F. A.;Sood, A. K.;Gill, P. S.
EphB 4是最大的跨膜受体酪氨酸激酶家族的成员，并且在轴突寻路和血管成熟中起关键作用。我们想确定EphB 4在卵巢癌中的生物学作用。应用免疫组织化学方法检测了7例正常卵巢组织和85例浸润性卵巢癌组织中EphB 4的表达。EphB 4在正常卵巢表面上皮中基本不表达，但在86%的卵巢癌中表达。EphB 4表达与疾病的晚期和腹水的存在显著相关。在单变量和多变量分析中，EphB 4的过表达均预测不良生存率。我们还研究了EphB 4在卵巢肿瘤细胞系中表达的生物学意义。与两种良性细胞系相比，测试的所有五种恶性卵巢肿瘤细胞系表达更高水平的EphB 4。用孕酮而不是雌激素治疗恶性而不是良性卵巢肿瘤细胞系，导致EphB 4水平降低90%，这与细胞存活率降低50%有关。通过特异性siRNA或反义寡核苷酸抑制EphB 4表达，通过激活半胱天冬酶-8诱导细胞凋亡，显著抑制肿瘤细胞活力，并且还抑制肿瘤细胞侵袭和迁移。此外，EphB 4反义显着抑制卵巢肿瘤异种移植物和肿瘤微血管系统在体内的生长。因此，抑制EphB 4可能在卵巢癌中具有预后和治疗效用。
EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma.
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影响因子：
3.8
作者：
Lee YC;Perren JR;Douglas EL;Raynor MP;Bartley MA;Bardy PG;Stephenson SA
通讯作者：
Stephenson SA
影响因子：
2.8
作者：
Wu, QH;Suo, ZH;Nesland, JM
通讯作者：
Nesland, JM
影响因子：
16
作者：
Gerety, SS;Wang, HU;Anderson, DJ
通讯作者：
Anderson, DJ
影响因子：
11.2
作者：
Xia, GB;Kumar, SR;Gill, PS
通讯作者：
Gill, PS
影响因子：
--
作者：
Stephenson, S A;Slomka, S;Hardingham, J E
通讯作者：
Hardingham, J E