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Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer
Breast Cancer Research and Treatment, 11/12/09
Fujikane T et al. – DNA methylation appears to be a common event in breast cancer, and the genes silenced by methylation could be useful targets for both diagnosis and therapy
Methods- Applied genomic screening to identify genes upregulated by demethylating agent 5-aza-2?-deoxycytidine (DAC) in human breast cancer cell line (MCF7)
- Identified 288 genes upregulated and 29 genes downregulated more than fivefold after treatment with DAC, and gene ontology analyses revealed the genes to be involved in immune responses, apoptosis, and cell differentiation
- Real-time PCR analysis of 10 genes silenced in MCF7 cells confirmed that they are upregulated by DAC, while bisulfite-pyrosequencing analysis confirmed that 9 of those genes were silenced by methylation
- Treating MCF7 cells with DAC restored induction of DFNA5 by p53, as well as by 2 other p53 family genes, p63? and p73?
- Introduction of NTN4 into MCF7 cells suppressed cell growth, indicating that NTN4 has tumor suppressive activity
- Primary breast cancers, we detected cancer-specific methylation of NTN4, PGP9.5, and DKK3, suggesting that methylation of these genes could be useful markers for diagnosis of breast cancer
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