Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8338767 | The Journal of Steroid Biochemistry and Molecular Biology | 2014 | 9 Pages |
Abstract
There is growing evidence that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) plays a role in breast cancer prevention and survival. It elicits a variety of antitumor activities like controlling cellular differentiation, proliferation and angiogenesis. Most of its biological effects are exerted via its nuclear receptor which acts as a transcriptional regulator. Here, we carried out a genome-wide investigation of the primary transcriptional targets of 1α,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1α,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1α,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1α,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1α,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1α,25(OH)2D3 treatment provides a resource of primary 1α,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells.
Keywords
TSSKEGGlog2 fold changeH3K4me3HNSCCVDREVDRqRT-PCRRNA-seqqPCRChIP-Seq1α,25(OH)2D31α,25-dihydroxyvitamin D3Quantitative PCRquantitative RT-PCRchromatin immunoprecipitationChIP-sequencingRNA-sequencingMutant p53Kyoto Encyclopedia of Genes and GenomesDAVIDTranscriptional start siteMarsresponse elementdatabase for annotation, visualization and integrated discoveryCHiPHead and neck squamous cell carcinomaVitamin D receptor
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Authors
Frauke Goeman, Francesca De Nicola, Paolo D'Onorio De Meo, Matteo Pallocca, Berardino Elmi, Tiziana Castrignanò, Graziano Pesole, Sabrina Strano, Giovanni Blandino, Maurizio Fanciulli, Paola Muti,