Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse

Bojie Dai, Oekyung Kim, Yingqiu Xie, Zhiyong Guo, Kexin Xu, Bin Wang, Xiangtian Kong, Jonathan Melamed, Hegang Chen, Charles J. Bieberich, Alexander D. Borowsky, Hsing Jien Kung, Guo Wei, Michael C. Ostrowski, Angela Brodie, Yun Qiu

研究成果: 雜誌貢獻文章同行評審

48 引文 斯高帕斯(Scopus)

摘要

The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human prostate xenograft CWR22. Here, we report that Etk is up-regulated in human prostate tumor specimens surveyed. Knocking down Etk expression by a specific small interfering RNA (siRNA) in prostate cancer cells attenuates cell proliferation, suggesting an essential role of Etk for prostate cancer cell survival and growth. Targeted expression of Etk in mouse prostate epithelium results in pathologic changes resembling human prostatic intraepithelial neoplasia, indicating that up-regulation of Etk may contribute to prostate cancer development. A marked increase of luminal epithelial cell proliferation was observed in the Etk transgenic prostate, which may be attributed in part to the elevated activity of Akt and signal transducers and activators of transcription 3 (STAT3). More interestingly, the expression level of acetyltransferase cyclic AMP-responsive element binding protein-binding protein (CBP) is also increased in the Etk transgenic prostate as well as in a prostate cancer cell line overexpressing Etk, concomitant with elevated histone 3 acetylation at lysine 18 (H3K18Ac). Down-modulation of Etk expression by a specific siRNA leads to a decrease of H3 acetylation in prostate cancer cell lines. Our data suggest that Etk may also modulate chromatin remodeling by regulating the activity of acetyltransferases, such as CBP. Given that Etk may exert its effects in prostate through modulation of multiple signaling pathways altered in human prostate cancer, the Etk transgenic mouse model may be a useful tool for studying the functions of Etk and identification of new molecular markers and drug targets relevant to human diseases.
原文英語
頁(從 - 到)8058-8064
頁數7
期刊Cancer Research
66
發行號16
DOIs
出版狀態已發佈 - 8月 15 2006
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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