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.