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The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

Oncogene volume 26, pages 4590–4595 (2007)Cite this article

Abstract

PSP94, for prostatic secretory protein of 94 amino acids, is secreted by the prostate gland and functions as a suppressor of tumor growth and metastasis. The expression of PSP94 is lost in advanced, hormone-refractory prostate cancer and this correlates with an increased expression of the Polycomb protein EZH2 (enhancer of zeste homolog 2), which represses transcription via trimethylation of histone H3 on Lys27 (H3K27). We show here that these events are causally related and that the MSMB gene, which encodes PSP94, is trimethylated on H3K27 in androgen-refractory, but not in androgen-sensitive prostate cancer cells. Chromatin immunoprecipitation experiments confirmed an association of EZH2 with the MSMB gene. The RNAi-mediated knockdown of EZH2 resulted in a loss of H3K27 trimethylation and an increased expression of the MSMB gene. Conversely, the overexpression of EZH2 was associated with a decreased expression of the MSMB gene. We also demonstrate that MSMB is additionally repressed in androgen-refractory prostate cancer cells by the hypoacetylation of histone H3K9 and the hypermethylation of a CpG island in the promoter region. Our data disclose a hitherto unexplored link between the putative oncogene EZH2 and the tumor suppressor PSP94, and show that MSMB is silenced by EZH2 in advanced prostate cancer cells.

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Acknowledgements

This work was financially supported by the Fund for Scientific Research-Flanders (Grant G.0290.05), a Flemish Concerted Research Action and the Prime Minister's office (IAP/V-05). Fabienne Withof provided expert technical assistance.

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  1. L Beke, M Nuytten and A Van Eynde: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Cell Biology, Laboratory of Biosignaling & Therapeutics, Faculty of Medicine, KULeuven, Leuven, Belgium

    L Beke, M Nuytten, A Van Eynde, M Beullens & M Bollen

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  1. L Beke
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  2. M Nuytten
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  3. A Van Eynde
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  4. M Beullens
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Correspondence to A Van Eynde.

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Beke, L., Nuytten, M., Van Eynde, A. et al. The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2. Oncogene 26, 4590–4595 (2007). https://doi.org/10.1038/sj.onc.1210248

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