1. ¹Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo Japan
2. ²Laboratory of Molecular Food Chemistry and Biochemistry, Department of Life Sciences, Faculty of Bioresources, Mie University, Kuriyamachiya-cho, Tsu, Mie, Japan
3. ³Nippon Boehringer Ingelheim Co. Ltd, Kawanishi Pharma Research Institute, Kawanishi, Hyogo, Japan

Correspondence: Dr T Matsuda, Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan. E-mail: tmatsuda@pharm.hokudai.ac.jp

Received 6 June 2006; Revised 22 January 2007; Accepted 13 February 2007; Published online 26 March 2007.

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 -estradiol (E2)-induced DUSP22 mRNA expression in estrogen receptor (ER)-positive breast cancer cells, whereas E2-induced phosphorylation and activation of ER was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. Furthermore, small-interfering RNA-mediated reduction of DUSP22 expression enhanced ER-mediated transcription and endogenous gene expression. In fact, DUSP22 associated with ER in vivo and both endogenous proteins interacted in ER-positive breast cancer T47D cells. These results strongly suggest that DUSP22 acts as a negative regulator of the ER-mediated signaling pathway.