Pharmacomethylomics: methylation profiling applied to drug resistance models

作者: Pauline de Graef , Geert Trooskens , Steven de Jong , Ate van der Zee , Herman Spolders

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摘要: A95 One major problem in the treatment of cancers using chemotherapeutic agents is occurrence resistance against compound used. Here we report a pilot study to investigate this more detail Pharmacomethylomics" approach. The model used current consists set three cell lines ("Glc4", "Tera" and "A2780") derived showing elevated concentrations compounds Doxorubicin Cisplatin culture.The methylation status promoter sequences 10 genes involved DNA repair pathways was investigated highly specific SybrGreen based real-time MSP. Each region represented by two different pairs primers. In vitro methylated as positive control for technical performance (single band agarose gels; single melting peak indicating expected temperature; no signal template controls) assays applied.Using described experimental set-up, could show that FancG (NM_004629), RAD9A (NM_004584), RecQL5 (NM_001003715), XRCC3 (NM_005432), HUS1 (NM_004507) at least three-fold higher level resistant compared their sensitive counterparts.The findings presented here indicate studying promoters may contribute better understanding development drug chemotherapy patients.

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