Transcriptional coactivator Drosophila eyes absent homologue 2 is up-regulated in epithelial ovarian cancer and promotes tumor growth.
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.
Zhang
Lin
L
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.
Yang
Nuo
N
Huang
Jia
J
Buckanovich
Ronald J
RJ
Liang
Shun
S
Barchetti
Andrea
A
Vezzani
Cristina
C
O'Brien-Jenkins
Ann
A
Wang
Jennifer
J
Ward
Michelle Renee
MR
Courreges
Maria C
MC
Fracchioli
Stefano
S
Medina
Angelica
A
Katsaros
Dionyssios
D
Weber
Barbara L
BL
Coukos
George
G
D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation
D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C106938:EYA2 protein, human; C501159:Eya2 protein, mouse; D017027:Protein Tyrosine Phosphatases