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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)8058-8064
Number of pages7
JournalCancer Research
Volume66
Issue number16
DOIs
Publication statusPublished - Aug 15 2006
Externally publishedYes

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Protein-Tyrosine Kinases
Prostate
Prostatic Neoplasms
Neoplasms
Acetyltransferases
Acetylation
Small Interfering RNA
Carrier Proteins
Cell Proliferation
Prostatic Intraepithelial Neoplasia
Cell Line
STAT3 Transcription Factor
Chromatin Assembly and Disassembly
Heterografts
Protein Binding
Cyclic AMP
Histones
Transgenic Mice
Lysine
Cell Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse. / Dai, Bojie; Kim, Oekyung; Xie, Yingqiu; Guo, Zhiyong; Xu, Kexin; Wang, Bin; Kong, Xiangtian; Melamed, Jonathan; Chen, Hegang; Bieberich, Charles J.; Borowsky, Alexander D.; Kung, Hsing Jien; Wei, Guo; Ostrowski, Michael C.; Brodie, Angela; Qiu, Yun.

In: Cancer Research, Vol. 66, No. 16, 15.08.2006, p. 8058-8064.

Research output: Contribution to journalArticle

Dai, B, Kim, O, Xie, Y, Guo, Z, Xu, K, Wang, B, Kong, X, Melamed, J, Chen, H, Bieberich, CJ, Borowsky, AD, Kung, HJ, Wei, G, Ostrowski, MC, Brodie, A & Qiu, Y 2006, 'Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse', Cancer Research, vol. 66, no. 16, pp. 8058-8064. https://doi.org/10.1158/0008-5472.CAN-06-1364
Dai, Bojie ; Kim, Oekyung ; Xie, Yingqiu ; Guo, Zhiyong ; Xu, Kexin ; Wang, Bin ; Kong, Xiangtian ; Melamed, Jonathan ; Chen, Hegang ; Bieberich, Charles J. ; Borowsky, Alexander D. ; Kung, Hsing Jien ; Wei, Guo ; Ostrowski, Michael C. ; Brodie, Angela ; Qiu, Yun. / Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse. In: Cancer Research. 2006 ; Vol. 66, No. 16. pp. 8058-8064.
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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.",
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AU - Dai, Bojie

AU - Kim, Oekyung

AU - Xie, Yingqiu

AU - Guo, Zhiyong

AU - Xu, Kexin

AU - Wang, Bin

AU - Kong, Xiangtian

AU - Melamed, Jonathan

AU - Chen, Hegang

AU - Bieberich, Charles J.

AU - Borowsky, Alexander D.

AU - Kung, Hsing Jien

AU - Wei, Guo

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AU - Brodie, Angela

AU - Qiu, Yun

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N2 - 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.

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