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Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand

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An Erratum to this article was published on 21 February 2012

Abstract

Mammalian MST2 kinase plays an important role in cell proliferation, survival, and apoptosis. In search of interacting proteins of MST2, we found that estrogen receptor α (ERα) co-immunoprecipitates with MST2 and its adaptor protein human Salvador (hSAV). Using reporter assays, we observed that overexpression of MST2 and hSAV leads to ligand-independent activation of ERα in human breast cancer MCF-7 cells, which was attenuated by the knockdown of hSAV. Furthermore, using truncated mutants of hSAV, we observed that the C terminus of hSAV is necessary and sufficient for the induction of ERα transactivation. The expression of hSAV and MST2 results in the phosphorylation of ERα at serine residues 118 and 167 and represses ERα expression. We then investigated the incidence of MST2 and ERα expression with other tumor biomarkers using commercially available tissue microarrays. Among 40 breast cancer samples analyzed, 60% (24 out of 40) expressed MST2. Nineteen among the 40 cases were MST2-positive and ERα-negative, implying a correlation between expressions of MST2 with loss of ERα in breast tumor samples. This study suggests that MST and hSAV act as novel co-regulators of ERα and may play an important role in breast cancer pathogenesis.

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Acknowledgements

This work was supported by grants from the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (2009-0084887) and BK21 to YJL.

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The authors declare no conflict of interests related to this study.

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Authors and Affiliations

  1. College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, 143-747, South Korea

    Yeomyung Park, Joonwoo Park, Wonchung Lim & YoungJoo Lee

  2. Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, South Korea

    Yonghee Lee

  3. Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Inchon, South Korea

    Byung-Chul Oh

  4. College of Medicine, Konkuk University, Seoul, South Korea

    ChanYoung Shin & Wansup Kim

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  1. Yeomyung Park
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Correspondence to YoungJoo Lee.

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Yeomyung Park and Joonwoo Park contributed equally to this study.

An erratum to this article is available at http://dx.doi.org/10.1007/s00109-012-0871-6.

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Park, Y., Park, J., Lee, Y. et al. Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand. J Mol Med 89, 181–191 (2011). https://doi.org/10.1007/s00109-010-0698-y

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  • DOI: https://doi.org/10.1007/s00109-010-0698-y

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