Abstract B17: Epigenetic regulation of NOTCH oncogenic signaling in breast cancer

Alterations in DNA methylation occur at different stages of cancer, including initiation, and may underlie up-regulation of genes with oncogenic functions. The NOTCH pathway is often overactive in breast cancer and plays roles in cancer development and progression. It is therefore a possible target for anti-cancer strategies. However, the mechanisms of NOTCH regulation in mammary carcinogenesis remain unclear which hinders the development of effective approaches to target this oncogenic pathway. Interestingly, certain dietary compounds such as polyphenols with a stilbenoid structure suppress the NOTCH signals in cancer and were shown in our study to modify epigenetic marks in genes positively regulating the pathway, including MAML2.In the present study, using two polyphenols, resveratrol from grapes and pterostilbene from blueberries, we investigate the implication of DNA methylation in regulation of NOTCH in breast cancer. Non-invasive MCF10CA1h and invasive MCF10CA1a human breast cancer cell lines were used as an experimental model. Following genome-wide DNA methylation analysis with Illumina 450K BeadChip array, pyrosequencing and QPCR were performed to assess methylation and expression of MAML2 and NOTCH target genes. Chromatin immunoprecipitation (ChIP) was applied to determine binding of epigenetic enzymes to MAML2 regulatory region. Depletion with siRNA was applied to establish functional link between MAML2 silencing and NOTCH activity.We found 4,293 CpG sites differen...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Genomics and Epigenomics Source Type: research