Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma

Int J Cancer. 2002 Dec 10;102(5):507-13. doi: 10.1002/ijc.10746.


The mitogen-activated protein kinase phosphatase-1, MKP-1 (CL100) is involved in inactivation of MAP-kinase pathways, regulation of stress-responses and suppression of apoptosis. We investigated expression of MKP-1 in 90 cases of primary ovarian tumors, 11 normal ovaries as well as 4 ovarian carcinoma cell lines. Immunohistochemical expression of MKP-1 protein was reduced in tissue from LMP tumors and invasive ovarian carcinomas compared to normal ovaries and cystadenomas. A moderate to strong expression of MKP-1 was detected in 57.6% of invasive ovarian carcinomas. In a descriptive univariate survival analysis, MKP-1 expression was a prognostic marker for shorter progression-free survival of patients with invasive ovarian carcinomas. Patients with carcinomas positive for MKP-1 had a median progression-free survival of only 18.3 months compared to 40.6 months for patients with carcinomas negative for MKP-1 (log-rank test, p = 0.019). Other prognostic parameters for progression-free survival were FIGO stage, grade and pT stage. In an exploratory multivariate analysis, we found that MKP-1 expression as well as FIGO stage and grade were independent prognostic factors for progression-free survival. In contrast to progression-free survival, we did not find any influence of MKP-1 expression on patient overall survival. We investigated expression and regulation of MKP-1 mRNA by Northern Blot in vitro using 4 ovarian carcinoma cell lines (SKOV-3, OVCAR-3, CAOV-3, OAW-42). MKP-1 mRNA was inducible by interleukin-1beta and tumor necrosis factor-alpha in SKOV-3 and OVCAR-3 cells, whereas CAOV-3 and OAW-42 expressed MKP-1 mRNA constitutively. In OVCAR-3 cells MKP-1 mRNA levels were strongly inducible upon treatment of cells with cisplatin. Our data indicate that MKP-1 is expressed in a subset of ovarian carcinomas and regulated by inflammatory mediators. Expression of MKP-1 may be associated with shorter progression-free survival times. Further studies are needed to determine whether MKP-1 expression is a clinically useful marker to estimate patient prognosis as well as the response to chemotherapy.

Publication types

  • Comparative Study

MeSH terms

  • Carcinoma / enzymology*
  • Carcinoma / pathology
  • Cell Cycle Proteins*
  • Cisplatin / pharmacology
  • Cystadenoma / enzymology
  • Dual Specificity Phosphatase 1
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Immunohistochemistry
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology
  • Ovary / enzymology
  • Phosphoprotein Phosphatases*
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • RNA, Messenger / biosynthesis
  • Retrospective Studies
  • Survival Analysis
  • Tumor Cells, Cultured


  • Cell Cycle Proteins
  • Immediate-Early Proteins
  • RNA, Messenger
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1
  • Protein Tyrosine Phosphatases
  • Cisplatin