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Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Oncogene volume 18, pages 3391–3398 (1999)Cite this article

Abstract

Prostate carcinoma (PCA) is the most frequently diagnosed malignancy in American men. PCA at advanced stages can both proliferate abnormally and resist apoptosis. Among the many known signal transduction pathways, phosphatidylinositide-3′OH kinase (PI3-kinase) has been shown to play an important role in cell survival and resistance to apoptosis. In this study, we investigate the involvement of Etk/Bmx, a newly discovered tyrosine kinase that is a substrate of PI3-kinase, in protection of prostate cancer cells from apoptosis. Parental LNCaP cells and two derivative cell lines, one overexpressing wild type Etk (Etkwt) and the other expressing a dominant negative Etk (EtkDN), were used to study the function of Etk. The cells were treated with photodynamic therapy (PDT), a newly approved cancer treatment which employs a photosensitizer and visible light to produce an oxidative stress in cells, often leading to apoptosis. Our results indicate that PDT induces apoptosis in LNCaP cells, as measured by DNA fragmentation and by cleavage of poly(ADP-ribose) polymerase (PARP), and moreover, the extent of apoptosis was much reduced in Etkwt cells as compared to LNCaP or EtkDN cells. Assay of overall cell viability confirmed that Etkwt cells were considerably less sensitive to PDT than were the parental LNCaP or EtkDN cells. Similar results were found in response to thapsigargin (TG). A specific inhibitor of PI3-kinase, LY294002, abolished Etk activity and markedly increased TG-induced PARP cleavage. The results suggest that Etk/Bmx is an efficient effector of PI3-kinase and that the newly described PI3-kinase/Etk pathway is involved in the protection of prostate carcinoma cells from apoptosis in response to PDT or TG.

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Acknowledgements

This research was supported by PHS grant P01 CA48735 to NL Oleinick and grants CA39207, CA57179 and DK52659 to H-J Kung, a grant from Gustavus and Louise Pfeiffer Research Foundation to Y Qiu, and Cancer Center Support Grant P30 CA43703.

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Author notes

  1. Liang-Yan Xue and Yun Qiu: LY Xue and Y Qiu contributed equally to this paper

Authors and Affiliations

  1. Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, Ohio, USA

    Liang-Yan Xue, Jin He & Nancy L Oleinick

  2. Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, Ohio, USA

    Yun Qiu & Hsing-Jien Kung

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  1. Liang-Yan Xue
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Xue, LY., Qiu, Y., He, J. et al. Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin. Oncogene 18, 3391–3398 (1999). https://doi.org/10.1038/sj.onc.1202687

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