title: Decreased total MKP-1 protein levels predict poor prognosis in breast cancer.
abstract: 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.
authors.affiliation: Department of Surgery, Cancer Center and Division of General & Gastroenterological Surgery, Kaohsiung Medical University Hospital, No. 100, Shiquan 1st Rd., Sanmin Dist., Kaohsiung City, 807, Taiwan, ROC. mifeho@kmu.edu.tw
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Chen
authors.forename: Shen-Nien
authors.initials: SN
authors.lastname: Wang
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Chen
authors.forename: Jinu-Huang
authors.initials: JH
authors.lastname: Su
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D016009:Chi-Square Distribution; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation / Q000379:methods; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D013629:Tamoxifen; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1