Decreased total MKP-1 protein levels predict poor prognosis in breast cancer.

Abstract

MKP-1 dephosphorylates and inactivates MAPKs, whose constitutive activations have been associated with human cancers. We found that total MKP-1 protein levels were decreased in 63.7 % of breast cancer tissues compared with the paired noncancerous breast tissues. Decreased MKP-1 protein levels were correlated with increased tumor stage and positive recurrence and were associated with poor survival, even when using a multivariate Cox regression model. Intriguingly, nuclear MKP-1 staining was positively correlated with ER status. In vitro, tamoxifen increased MKP-1 expression in ER-positive but not ER-negative breast cancer cells. ER-specific siRNA was able to attenuate tamoxifen-induced MKP-1 expression. Furthermore, tamoxifen prolonged the duration of MKP-1 elevation and the binding time of ER to the promoter of the MKP-1/DUSP-1 gene compared with estrogen. Our results suggest that alterations of MKP-1 may serve as a prognostic factor in breast cancer. In addition, the regulation of MKP-1 may be related to the ER.