title: Hypothesis: Activation of rapid signaling by environmental estrogens and epigenetic reprogramming in breast cancer.
abstract: Environmental and lifestyle factors are considered significant components of the increasing breast cancer risk in the last 50 years. Specifically, exposure to environmental endocrine disrupting compounds is correlated with cancer susceptibility in a variety of tissues. In both human and rodent models, the exposure to ubiquitous environmental estrogens during early life has been shown to disrupt normal mammary development and cause permanent adverse effects. Recent studies indicate that environmental estrogens not only have the ability to disrupt estrogen receptor (ER) signaling, but can also reprogram the epigenome by altering DNA and histone methylation through rapid, nongenomic ER actions. We have observed xenoestrogen-mediated activation of several nongenomic signaling pathways and have identified a target for epigenetic reprogramming in MCF-7 breast cancer cells. These observations, in addition to data from the literature, support the hypothesis that activation of rapid signaling by environmental estrogens can lead to epigenetic reprogramming and contribute to the progression of breast cancer.
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, United States.
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Treviño
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, United States.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, United States. Electronic address: cwalker@ibt.tamhsc.edu.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Walker
mesh_terms: D000367:Age Factors; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D065150:Cellular Reprogramming / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002274:Carcinogens, Environmental; D052244:Endocrine Disruptors; D004967:Estrogens
keywords: Breast cancer; Environmental estrogens; Epigenetics; Histone modifiers