Systematic name M2065
Brief description Genes down-regulated in MCF7 cells (breast cancer) upon knockdown of CLOCK [GeneID=9575] by RNAi that also belong to the highest confidence network (according to Ingenuity Pathway Analysis).
Full description or abstract The transcription factors responsible for maintaining circadian rhythm influence a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. To evaluate this hypothesis, we conducted a genetic and epigenetic association study, as well as a transcriptional profiling array and a pathway-based network analysis. We report significant correlations between single nucleotide polymorphisms associated with the central circadian regulator CLOCK and breast cancer risk, with apparent effect modification by estrogen receptor/progesterone receptor status. We also found that hypermethylation in the CLOCK promoter reduced the risk of breast cancer, and lower levels of CLOCK expression were documented in healthy controls relative to normal or tumor tissue from patients with breast cancer. Finally, we silenced CLOCK in vitro and performed a whole-genome expression microarray and pathway analysis, which identified a cancer-relevant network of transcripts with altered expression following CLOCK gene knockdown. Our findings support the hypothesis that circadian genes influence tumorigenesis, and identify a set of circadian gene variants as candidate breast cancer susceptibility biomarkers.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 20124474   Authors: Hoffman AE,Yi CH,Zheng T,Stevens RG,Leaderer D,Zhang Y,Holford TR,Hansen J,Paulson J,Zhu Y
Exact source Table 2: Fold change < 0
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Source species Homo sapiens
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