Decreased Total MKP-1 Protein Levels Predict Poor Prognosis in Breast Cancer
Decreased Total MKP-1 Protein Levels Predict Poor Prognosis in Breast Cancer
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DOI：
10.1007/s00268-012-1608-y
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发表时间：
2012-08-01
影响因子：
2.6
通讯作者：
Yeh, Yao-Tsung
中科院分区：
文献类型：
--
作者：
Hou, Ming-Feng;Chang, Chien-Wei;Yeh, Yao-Tsung
MKP-1使MAPKs去磷酸化和失活，MAPKs的组成性激活与人类癌症有关。我们发现，与配对的非癌乳腺组织相比，63.7%的乳腺癌组织中的总MKP-1蛋白水平降低。MKP-1蛋白水平降低与肿瘤分期增加和阳性复发相关，与生存率差相关，即使使用多变量考克斯回归模型。有趣的是，核MKP-1染色与ER状态呈正相关。在体外，他莫昔芬增加MKP-1在ER阳性而非ER阴性乳腺癌细胞中的表达。ER特异性siRNA能够减弱他莫昔芬诱导的MKP-1表达。此外，与雌激素相比，他莫昔芬延长了MKP-1升高的持续时间和ER与MKP-1/DUSP-1基因启动子的结合时间。此外，MKP-1的调节可能与ER有关。
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.