MP45-04 PATERNALLY EXPRESSED GENE-10 PROMOTES CELL GROWTH AND INVASION OF BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2016MP45-04 PATERNALLY EXPRESSED GENE-10 PROMOTES CELL GROWTH AND INVASION OF BLADDER CANCER Yoshihisa Kawai, Shusuke Akamatsu, Tetsutaro Hayashi, Eliana Beraldi, Fan Zhang, Roland Seiler, Jeffrey Leong, Htoo Oo, Igor Moskalev, Ladan Fazli, Hideyasu Matsuyama, Peter Black, Colin Collins, and Martin Gleave Yoshihisa KawaiYoshihisa Kawai More articles by this author , Shusuke AkamatsuShusuke Akamatsu More articles by this author , Tetsutaro HayashiTetsutaro Hayashi More articles by this author , Eliana BeraldiEliana Beraldi More articles by this author , Fan ZhangFan Zhang More articles by this author , Roland SeilerRoland Seiler More articles by this author , Jeffrey LeongJeffrey Leong More articles by this author , Htoo OoHtoo Oo More articles by this author , Igor MoskalevIgor Moskalev More articles by this author , Ladan FazliLadan Fazli More articles by this author , Hideyasu MatsuyamaHideyasu Matsuyama More articles by this author , Peter BlackPeter Black More articles by this author , Colin CollinsColin Collins More articles by this author , and Martin GleaveMartin Gleave More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.281AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have recently identified that paternally expressed gene-10 (PEG10) promotes cell cycle progression in the context of TP53 and RB1 loss in neuroendocrine prostate cancer. Based on the evidence that TP53 mutations and RB1 inactivation are more prevalent in muscle invasive bladder cancer (MIBC), it is possible that PEG10 may contribute to the progression and prognosis of MIBC. To test this hypothesis, we characterized PEG10 function in bladder cancer and evaluated if PEG10 can be a novel therapeutic target for these cancers. METHODS PEG10 gene expression of tumor samples was analyzed using the cancer genome atlas (TCGA) cohort. The PEG10 expression in several bladder cancer cell lines was assessed by Western blot analysis and quantitative reverse transcription-PCR (qRT-PCR). Silencing of PEG10 in vitro was achieved using siRNA. The in vivo effect of PEG10 antisense oligonucleotide (ASO) treatment was assessed in the T24 orthotopic bladder cancer model. RESULTS Higher mRNA level of PEG10 was significantly associated with poorer disease-free survival after cystectomy in 131 patients in the TCGA, Nature 2014 cohort. We examined PEG10 expression in a panel of 12 bladder cancer cell lines by Western blot. UM-UC14 showed the highest PEG10 expression, and T24 showed higher PEG10 expression than the other bladder cancer cell lines. Similar results were confirmed by qRT-PCR. PEG10 transient knockdown using two independent siRNAs resulted in significant growth suppression in UM-UC14 (RB1inactivatedTP53mut) and T24 (RB1wtTP53mut) cells. PEG10 knockdown induced higher expression of key cell cycle dependent kinase inhibitors p21 and p27 than observed in the control cells. Conversely, forced PEG10 RF1b/2 isoform over-expression induced cell growth in UC14 and T24 cells. Furthermore, UM-UC14 cell invasion was significantly decreased with PEG10 transient knockdown. Using BrdU incorporation assay after cell cycle synchronization by double-thymidine block, we found that PEG10 drove cell cycle progression from G0/G1. In the orthotopic bladder cancer model, systemic PEG10-ASO administration to athymic nude mice delayed tumor progression in T24 cells. CONCLUSIONS We have demonstrated that PEG10 promotes bladder cancer progression. Inhibition of PEG10 may be a novel treatment strategy for a subset of bladder cancer. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e608 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yoshihisa Kawai More articles by this author Shusuke Akamatsu More articles by this author Tetsutaro Hayashi More articles by this author Eliana Beraldi More articles by this author Fan Zhang More articles by this author Roland Seiler More articles by this author Jeffrey Leong More articles by this author Htoo Oo More articles by this author Igor Moskalev More articles by this author Ladan Fazli More articles by this author Hideyasu Matsuyama More articles by this author Peter Black More articles by this author Colin Collins More articles by this author Martin Gleave More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...