MPP3 inactivation by promoter CpG islands hypermethylation in colorectal carcinogenesis
| Autor: | Hao Wang, Si Cheng, Yali Zhang, Guoli Wei, Side Liu, Yu Zhou, Xiao Feng, Wenkai Tan, Ke-quan Chen, Shicai Ye |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Deleted in Colorectal Cancer Colorectal cancer Down-Regulation Gene Expression Biology law.invention law Cell Line Tumor Genetics medicine Humans Epigenetics Gene Silencing Promoter Regions Genetic Nuclear Proteins General Medicine Methylation DNA Methylation Middle Aged medicine.disease Molecular biology Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Oncology CpG site Cell culture DNA methylation Suppressor CpG Islands Female Colorectal Neoplasms HT29 Cells Transcription Factors |
| Zdroj: | Cancer biomarkers : section A of Disease markers. 11(2-3) |
| ISSN: | 1875-8592 |
| Popis: | Background: The Drosophila discs large tumor suppressor homologue-3 (MPP3), a putative tumor suppressor involved in cell adhesion and cell polarity, isfrequently inactivated in several carcinomas due to promoter hypermethylation. Thealteration of MPP3 methylation in colorectal carcinogenesis has not been investigated. Objective: To determine the role of inactivated MPP3 in colorectal tumorigenesis and the potential clinical application as a novel epigenetic marker. Methods: We measured MPP3 mRNA expression and promoter methylation in 6 colorectal cancer cell lines, 23 primary colorectal carcinomas and corresponding non-cancerous tissues. The correlations between MPP3 expression, DNA methylation and clinicopathological characteristics were evaluated. Results: Loss of MPP3 expression was observed in 2 of 6 (33.3%) colorectal cancer cell lines and 10 of 23 (43.5%) primary colorectal carcinomas. MPP3 promoter hypermethylation also occurred in the same colorectal cancer cell lines (SW1116 and LoVo) and 9 of 23 (39.1%) primary colorectal carcinomas. Among tumors loss of MPP3 mRNA expression, the promoter hypermethylation ratewas 80%, which was significantly higher than tumors withover-expressed MPP3 (7.7%, P = 0.001). After treated with 5-aza-dC, two cell lines (SW1116 and LoVo) revealed significant restoration of MPP3 expression. MPP3 promoter methylation was also significantly higher in advanced colorectal carcinoma (57.1%) compared with early stage tumor (11.1%). Conclusion: These preliminary data suggested that epigenetic inactivation of MPP3 frequently occurred during the development of colorectal cancer and might also be a potential biomarker for molecular classification of colorectal cancer patients. |
| Databáze: | OpenAIRE |
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