Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity

Abstract

SummaryWe established the role for epigenetics in regulation of NOTCH signaling in breast cancer. This may constitute a common mechanism of activation of oncogenic signals. Our study provides support for epigenetic-targeting strategies in anticancer approaches.

Stilbenoid‐Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor

“…The microarray data for MCF10CA1h cells upon 4‐day exposure to RSV are presented in the current manuscript for the first time. The microarray data on hypermethylated genes upon 9‐day RSV exposure in both MCF10CA1h and MCF10CA1a breast cancer cell lines were previously reported by the authors’ group and re‐analyzed in the current manuscript with focus on hypomethylated genes in response to RSV. The microarray data are available from Gene Expression Omnibus [accession numbers: GSE80794 for MCF10CA1h (9‐day exposure) and MCF10CA1a (9‐day exposure) breast cancer cells; GSE113299 for MCF10A mammary epithelial cells; GSE132670 for MCF10CA1h breast cancer cells (4‐day exposure)].…”

“…DNA from cells treated with ethanol as a vehicle control and from cells exposed to RSV was isolated using standard phenol:chloroform extraction protocol and subjected to genome‐wide DNA methylation analysis using Infinium HumanMethylation 450K BeadChip, as described previously in detail . Hybridization and scanning were performed in the Genomics Facility of University of Chicago, IL.…”

“…DNA, isolated using standard phenol:chloroform extraction protocol, was treated with sodium bisulfite as previously described . HotStar Taq DNA polymerase (Qiagen) and biotinylated primers were used to amplify bisulfite converted promoter sequences of the selected genes (please see Table S1A, Supporting Information, for primer sequences).…”

“…Our recent genome‐wide investigation into DNA methylation patterns demonstrates that loci‐specific increases and decreases in DNA methylation occur in breast cancer cells in response to RSV . We specifically described genes that gain methylation and are enriched with oncogenic pathways . In the present study, we extended our investigation by performing Illumina Infinium Human Methylation 450K BeadChip microarray to test time‐dependent genome‐wide effects and focused on genes that lose methylation upon exposure to RSV and fall into a category of potential TSGs, in lowly invasive MCF10CA1h and highly invasive MCF10CA1a breast cancer cells.…”

“…Our recent genome‐wide investigation into DNA methylation patterns demonstrates that loci‐specific increases and decreases in DNA methylation occur in breast cancer cells in response to RSV . We specifically described genes that gain methylation and are enriched with oncogenic pathways .…”