title: Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse.
abstract: 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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Bojie
authors.initials: B
authors.lastname: Dai
authors.forename: Oekyung
authors.initials: O
authors.lastname: Kim
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Xie
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Kexin
authors.initials: K
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Kong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Hegang
authors.initials: H
authors.lastname: Chen
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Bieberich
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ostrowski
authors.forename: Angela
authors.initials: A
authors.lastname: Brodie
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics*; D017384:Sequence Deletion; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases