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DUSP22/LMW-DSP2 regulates estrogen receptor-α-mediated signaling through dephosphorylation of Ser-118

Oncogene volume 26, pages 6038–6049 (2007)Cite this article

Abstract

In the previous study, we demonstrated the involvement of dual specificity phosphatase 22 (DUSP22/LMW-DSP2) in regulating the leukemia inhibitory factor/interleukin-6/signal transducer and activator of transcription 3-mediated signaling pathway. In this study, we show β-estradiol (E2)-induced DUSP22 mRNA expression in estrogen receptor α (ERα)-positive breast cancer cells, whereas E2-induced phosphorylation and activation of ERα was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. Furthermore, small-interfering RNA-mediated reduction of DUSP22 expression enhanced ERα-mediated transcription and endogenous gene expression. In fact, DUSP22 associated with ERα in vivo and both endogenous proteins interacted in ERα-positive breast cancer T47D cells. These results strongly suggest that DUSP22 acts as a negative regulator of the ERα-mediated signaling pathway.

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Abbreviations

DUSP:

dual specificity phosphatase

ER:

estrogen receptor

E2:

β-estradiol

GST:

glutathione-S-transferase

LMW-DSP:

low molecular weight-dual specificity phosphatase

LUC:

luciferase

PCR:

polymerase chain reaction

RT:

reverse transcription

siRNA:

small interfering RNA

STAT:

signal transducer and activator of transcription

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Acknowledgements

This study was supported in part by Industrial Technology Research Grant Program in 2005 from New Energy and Industrial Technology Development organization (NEDO) of Japan.

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    Y Sekine, O Ikeda, Y Hayakawa, S Tsuji, S Imoto & T Matsuda

  2. Department of Life Sciences, Laboratory of Molecular Food Chemistry and Biochemistry, Faculty of Bioresources, Mie University, Kuriyamachiya-cho, Tsu, Mie, Japan,

    N Aoki

  3. Nippon Boehringer Ingelheim Co. Ltd, Kawanishi Pharma Research Institute, Kawanishi, Hyogo, Japan

    K Sugiyama

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  1. Y Sekine
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Correspondence to T Matsuda.

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Sekine, Y., Ikeda, O., Hayakawa, Y. et al. DUSP22/LMW-DSP2 regulates estrogen receptor-α-mediated signaling through dephosphorylation of Ser-118. Oncogene 26, 6038–6049 (2007). https://doi.org/10.1038/sj.onc.1210426

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