Exp Mol Med.
2012 May;44(5):356-362.
The mitogen-activated protein kinase phosphatase-1 (MKP-1) gene is a potential methylation biomarker for malignancy of breast cancer
- Affiliations
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- 1Department of Surgery, School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- 2Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. glycosamine@yahoo.com.tw
- 3Division of General and Gastroenterological Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
- 4Department of Biomedical Science and Environmental Biology, Graduate Institute of Natural Products, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- 5Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 807, Taiwan.
- 6Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- 7Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 807, Taiwan. glycosamine@yahoo.com.tw
- 8Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- 9National Sun Yat-Sen University-Kaohsiung Medical University, Joint Research Center, Kaohsiung 807, Taiwan.
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.
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