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c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

Oncogene volume 25, pages 7212–7223 (2006)Cite this article

Abstract

Androgens and the androgen receptor (AR) are involved in the growth and progression of prostate cancer. Our previous studies suggest that the proto-oncoprotein c-Jun is an AR coactivator that stimulates AR transactivation by mediating receptor dimerization and subsequent DNA binding. To study the physiological relevance of this c-Jun activity on AR, we have generated stable LNCaP cell lines expressing different levels of c-Jun. These cell lines exhibit a direct correlation between endogenous c-Jun levels and AR transcriptional activity and expression of endogenous androgen-regulated genes. Disruption by antisense RNA of endogenous c-Jun expression in LNCaP cells strongly compromises the androgen-dependent proliferation of these cells. In contrast, expression of a c-Jun mutant, which is fully active in coactivation of AR but deficient in AP-1 transactivation, significantly enhances androgen-dependent proliferation. This finding indicates that the coactivation function of c-Jun is sufficient for regulating androgen-induced growth of LNCaP cells. c-Jun also enhances AR transactivtion in androgen-independent LNCaP cells, which closely mimic hormone-refractory prostate cancer cells in gene expression and growth behavior. Importantly, siRNA-mediated repression of endogenous c-Jun expression results in markedly reduced growth of these cells, strongly suggesting an important biological role for c-Jun in hormone-refractory prostate cancer.

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Acknowledgements

We thank Dr S Leisner for critical reading of the manuscript. This work was supported by grants from National Institutes of Health and Ohio Cancer Research Associates.

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Author notes

  1. S-Y Chen

    Present address: Harvard Medical School, 330 Brookline Avenue, Boston, MA, USA

  2. C J Fisher & Z Zheng

    Present address: Medical University of Ohio, 3000 Arlington Avenue, Toledo, OH, USA

  3. J Omwancha

    Present address: Johns Hopkins University, 615 North Wolfe St., Baltimore, MD, USA

  4. S-Y Chen and C Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Sciences, University of Toledo, Toledo, OH, USA

    S-Y Chen, C Cai, C J Fisher, Z Zheng, J Omwancha, C-L Hsieh & L Shemshedini

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Correspondence to L Shemshedini.

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Chen, SY., Cai, C., Fisher, C. et al. c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation. Oncogene 25, 7212–7223 (2006). https://doi.org/10.1038/sj.onc.1209705

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