So Wai-Kin, Cheng Jung-Chien, Fan Qianlan, Wong Alice S T, Huntsman David G, Gilks C Blake, Leung Peter C K
Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
School of Biological Sciences, University of Hong Kong, Hong Kong, China.
FEBS Lett. 2015 Jan 30;589(3):302-9. doi: 10.1016/j.febslet.2014.12.012. Epub 2014 Dec 20.
Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase signaling. Our Human Exonic Evidence-Based Oligonucleotide (HEEBO) microarray results showed that the mRNA levels of SPRY2, but not of SPRY1 or SPRY4, are down-regulated in high-grade serous ovarian carcinoma (HGSC) tissues and epithelial ovarian cancer (EOC) cell lines. Molecular inversion probe (MIP) copy number analysis showed the deletion of the SPRY2 locus in HGSC. Overexpression of SPRY2 reduced EGF-induced cell invasion by attenuating EGF-induced E-cadherin down-regulation. Moreover, a positive correlation between SPRY2 and E-cadherin protein levels was observed in HGSC tissues. This study reveals the loss of SPRY2 in HGSC and indicates an important tumor-suppressive role for SPRY2 in mediating the stimulatory effect of EGF on human EOC progression.
Sprouty（SPRY）蛋白是已被充分表征的抑制受体酪氨酸激酶信号传导的因子。我们基于人类外显子证据的寡核苷酸（HEEBO）微阵列结果显示，在高级别浆液性卵巢癌（HGSC）组织和上皮性卵巢癌（EOC）细胞系中，SPRY2的mRNA水平下调，而SPRY1或SPRY4的mRNA水平未下调。分子倒置探针（MIP）拷贝数分析显示HGSC中SPRY2基因座缺失。SPRY2的过表达通过减弱表皮生长因子（EGF）诱导的E-钙黏蛋白下调来降低EGF诱导的细胞侵袭。此外，在HGSC组织中观察到SPRY2与E-钙黏蛋白蛋白水平呈正相关。本研究揭示了HGSC中SPRY2的缺失，并表明SPRY2在介导EGF对人EOC进展的刺激作用中具有重要的肿瘤抑制作用。
