Gene Set: CHENG_IMPRINTED_BY_ESTRADIOL

Standard name CHENG_IMPRINTED_BY_ESTRADIOL
Systematic name M19202
Brief description Genes whose CpG islands became hypermethylated in breast progenitor cells pre-exposed to estradiol [PubChem=5757].
Full description or abstract Estrogen imprinting is used to describe a phenomenon in which early developmental exposure to endocrine disruptors increases breast cancer risk later in adult life. We propose that long-lived, self-regenerating stem and progenitor cells are more susceptible to the exposure injury than terminally differentiated epithelial cells in the breast duct. Mammospheres, containing enriched breast progenitors, were used as an exposure system to simulate this imprinting phenomenon in vitro. Using MeDIP-chip, a methylation microarray screening method, we found that 0.5% (120 loci) of human CpG islands were hypermethylated in epithelial cells derived from estrogen-exposed progenitors compared with the non-estrogen-exposed control cells. This epigenetic event may lead to progressive silencing of tumor suppressor genes, including RUNX3, in these epithelial cells, which also occurred in primary breast tumors. Furthermore, normal tissue in close proximity to the tumor site also displayed RUNX3 hypermethylation, suggesting that this aberrant event occurs in early breast carcinogenesis. The high prevalence of estrogen-induced epigenetic changes in primary tumors and the surrounding histologically normal tissues provides the first empirical link between estrogen injury of breast stem/progenitor cells and carcinogenesis. This finding also offers a mechanistic explanation as to why a tumor suppressor gene, such as RUNX3, can be heritably silenced by epigenetic mechanisms in breast cancer.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18339859   Authors: Cheng AS,Culhane AC,Chan MW,Venkataramu CR,Ehrich M,Nasir A,Rodriguez BA,Liu J,Yan PS,Quackenbush J,Nephew KP,Yeatman TJ,Huang TH
Exact source Table 1S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform Human_NCBI_Gene_ID
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Version history 3.0: First introduced

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