title: The mitogen-activated protein kinase phosphatase-1 (MKP-1) gene is a potential methylation biomarker for malignancy of breast cancer.
abstract: The mitogen-activated protein kinase (MAPK) phosphatase- 1 (MKP-1) belongs to the MAPK cascades which are central to cell proliferation and apoptosis. The carcinogenic role of MKP-1 has been reported in many types of cancer but it has rarely been investigated in breast cancer. The present study was designed to evaluate the MKP-1 mRNA expression and its possible regulation by methylation of MKP-1 promoter in the model of several breast cancer cell lines and tissues as well as controls. Our data demonstrate MKP-1 mRNA expression significantly decreased in five breast cancer cell lines compared to breast controls (P<0.01). Using the methylation-specific PCR (MSP) analysis, the unmethylated reaction (U) is dominant in both normal cell lines and benign breast tumors (100% vs. 86.2%), whereas the methylated reaction (M) is dominant in both breast cancer cell lines and invasive breast tumors (100% vs. 57.2%). In terms of methylation ratio (M/M+U), methylation level in MKP-1 promoter is significantly higher in the invasive breast tumor tissues (n = 152) than in benign breast tumor tissues (n = 29) (P<0.0001). Assessing the methylation ratio of the promoter of MKP-1 gene to diagnose the breast malignancy (invasive vs. benign), the area under the receiver- operating characteristic (ROC) curve was 0.809 (95% CI: 0.711-0.906, P<0.001). The best performance for this prediction has a sensitivity of 76.32% and a specificity of 82.76% at the cutoff value of 0.38. Taken together, we firstly demonstrated that the promoter methylation of MKP-1 gene is a potential breast cancer biomarker for breast malignancy.
authors.affiliation: Department of Surgery, School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Chen
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Huang
authors.forename: Pei-Yung
authors.initials: PY
authors.lastname: Nien
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1