Zhang Lin, Yang Nuo, Huang Jia, Buckanovich Ronald J, Liang Shun, Barchetti Andrea, Vezzani Cristina, O'Brien-Jenkins Ann, Wang Jennifer, Ward Michelle Renee, Courreges Maria C, Fracchioli Stefano, Medina Angelica, Katsaros Dionyssios, Weber Barbara L, Coukos George
Abramson Family Cancer Research Institute, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Cancer Res. 2005 Feb 1;65(3):925-32.
Epithelial ovarian cancer is the most frequent cause of gynecologic malignancy-related mortality in women. To identify genes up-regulated in ovarian cancer, PCR-select cDNA subtraction was done and Drosophila Eyes Absent Homologue 2 (EYA2) was isolated as a promising candidate. The transcriptional coactivator eya controls essential cellular functions during organogenesis of Drosophila. EYA2 mRNA was found to be up-regulated in ovarian cancer by real-time reverse transcription-PCR, whereas its protein product was detected in 93.6% of ovarian cancer specimens by immunohistochemistry (n = 140). EYA2 was amplified in 14.8% of ovarian carcinomas, as detected by array-based comparative genomic hybridization (n = 88). Most importantly, EYA2 overexpression was significantly associated with short overall survival in advanced ovarian cancer (n = 99, P = 0.0361). EYA2 was found to function as transcriptional activator in ovarian cancer cells by Gal4 assay and to promote tumor growth in vivo in xenograft models. Therefore, this study suggests an important role of EYA2 in ovarian cancer and its potential application as a therapeutic target.
上皮性卵巢癌是女性妇科恶性肿瘤相关死亡的最常见原因。为了鉴定在卵巢癌中上调的基因，进行了PCR选择性cDNA消减，并分离出果蝇无眼同源物2（EYA2）作为一个有前景的候选基因。转录共激活因子eya在果蝇器官发生过程中控制重要的细胞功能。通过实时逆转录PCR发现EYA2 mRNA在卵巢癌中上调，而通过免疫组织化学在93.6%的卵巢癌标本中检测到其蛋白质产物（n = 140）。通过基于阵列的比较基因组杂交检测（n = 88），在14.8%的卵巢癌中检测到EYA2扩增。最重要的是，在晚期卵巢癌中（n = 99，P = 0.0361），EYA2过表达与总生存期短显著相关。通过Gal4检测发现EYA2在卵巢癌细胞中起转录激活因子的作用，并在异种移植模型中促进体内肿瘤生长。因此，本研究表明EYA2在卵巢癌中起重要作用及其作为治疗靶点的潜在应用价值。
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