BACKGROUND: MKP-1 dephosphorylates and inactivates MAPKs, whose constitutive activations have been associated with human cancers. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND:MKP-1 dephosphorylates and inactivates MAPKs, whose constitutive activations have been associated with humancancers. RESULTS: 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. CONCLUSIONS: 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.
Authors: Carsten Denkert; Wolfgang D Schmitt; Stefan Berger; Angela Reles; Sören Pest; Antje Siegert; Werner Lichtenegger; Manfred Dietel; Steffen Hauptmann Journal: Int J Cancer Date: 2002-12-10 Impact factor: 7.396
Authors: S Chattopadhyay; R Machado-Pinilla; C Manguan-García; C Belda-Iniesta; C Moratilla; P Cejas; J A Fresno-Vara; J de Castro-Carpeño; E Casado; M Nistal; M Gonzalez-Barón; R Perona Journal: Oncogene Date: 2006-02-06 Impact factor: 9.867
Authors: Andreas Vogt; Peter R McDonald; Aletheia Tamewitz; Rachel P Sikorski; Peter Wipf; John J Skoko; John S Lazo Journal: Mol Cancer Ther Date: 2008-02-01 Impact factor: 6.261