The mitogen-activated protein kinase phosphatase-1 (MKP-1) gene is a potential methylation biomarker for malignancy of breast cancer.
- Author:
Fang Ming CHEN
1
;
Hsueh Wei CHANG
;
Sheau Fang YANG
;
Ya Fang HUANG
;
Pei Yung NIEN
;
Yao Tsung YEH
;
Ming Feng HOU
Author Information
1. Department of Surgery, School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
biological markers;
breast neoplasms;
DNA methylation;
DUSP1 protein, human;
epigenesis, genetic
- MeSH:
*Breast Neoplasms/diagnosis/genetics/metabolism;
Cell Line, Tumor;
DNA Methylation/*genetics;
Dual Specificity Phosphatase 1/genetics/*metabolism;
Female;
Gene Expression Regulation, Neoplastic;
Humans;
*Promoter Regions, Genetic;
ROC Curve;
Sensitivity and Specificity;
Tumor Markers, Biological
- From:Experimental & Molecular Medicine
2012;44(5):356-362
- CountryRepublic of Korea
- Language:English
-
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.
