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EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer
Author(s) -
Kumagai Jinpei,
Urano Tomohiko,
Ogushi Tetsuo,
Takahashi Satoru,
HorieInoue Kuniko,
Fujimura Tetsuya,
Azuma Kotaro,
Muramatsu Masami,
Ouchi Yasuyoshi,
Kitamura Tadaichi,
Inoue Satoshi
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23982
Subject(s) - bladder cancer , immunostaining , cancer , cancer research , tumor progression , prostate cancer , immunohistochemistry , cell growth , pathology , biology , in vivo , small interfering rna , cell , medicine , transfection , cell culture , genetics , microbiology and biotechnology
Upregulation of EBAG9 expression has been observed in several malignant tumors such as advanced breast and prostate cancers, indicating that EBAG9 may contribute to tumor proliferation. In the present study, we assess the role of EBAG9 in bladder cancer. We generated human bladder cancer EJ cells stably expressing FLAG‐tagged EBAG9 (EJ‐EBAG9) or empty vector (EJ‐vector), and investigated whether EBAG9 overexpression modulates cell growth and migration in vitro as well as the in vivo tumor formation of EJ transfectants in xenograft models of BALB/c nude mice. EBAG9 overexpression promoted EJ cell migration, while the effect of EBAG9 to cultured cell growth was rather minimal. Tumorigenic experiments in nude mice showed that the size of EJ‐EBAG9‐derived tumors was significantly larger than EJ‐vector‐derived tumors. Loss‐of‐function study for EBAG9 using small interfering RNA (siRNA) in xenografts with parental EJ cells showed that the intra‐tumoral injection of EBAG9 siRNA markedly reduced the EJ tumor formation compared with control siRNA. Furthermore, immunohistochemical study for EBAG9 expression was performed in 60 pathological bladder cancer specimens. Intense and diffuse cytoplasmic immunostaining was observed in 45% of the bladder cancer cases. Positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients ( p = 0.0001) and it was an independent prognostic predictor for disease‐specific survival in multivariate analysis ( p = 0.003). Our results indicate that EBAG9 would be a crucial regulator of tumor progression and a potential prognostic marker for bladder cancer. © 2008 Wiley‐Liss, Inc.