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EDRI Federal Project Inventory:
70515-01 Environmental Estrogens and Breast Cancer
- Sponsor Organization: NIH/NCI
- Project Title: 70515-01 ENVIRONMENTAL ESTROGENS AND BREAST CANCER
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Many compounds used in our industrial society, including
insecticides, plasticizers, dioxins, and other xenobiotics,can be
classified as "environmental estrogens." Recent clinical
epidemiological studies are split as to whetherenvironmental estrogens
contribute to the observed increases in breast cancer incidence. Key
to understanding therelationship of environmental estrogens to breast
cancer is their mechanism of action whether they act directly
throughthe estrogen receptor or whether they produce estrogen-like
effects and alter breast cell biology by other mechanisms. Itis
critical to know whether compounds that bind to estrogen receptor
poorly still have estrogenic effects. Also, there is aneed for a more
effective way to screen compounds for estrogenic and anti-estrogenic
effects on the human breast. Thispilot project addresses these issues
by focusing on model non-steroidal estrogens, the Doisynolic/Allenolic
compounds.Like the multitude of potential environmental estrogens they
represent, these compounds demonstrate potent biologicaleffects, yet
bind to estrogen receptor poorly. Also they have a distinct history of
differing potencies in humans versusanimal species. Thus, they are
ideally positioned to address these important and current issues
regarding environmentalestrogens and breast cancer etiology. The
applicant's goal is to test the hypothesis that Doisynolic/Allenolic
acids, inspite of low affinity for estrogen receptor, mediate their
estrogenic effects through the classic estrogen receptor. We willuse
assays for each of the molecular functions of estrogen receptor. In
addition, the applicant will determine the receptordependence for each
mechanism of gene regulation. The applicant will evaluate both
estrogen receptor mediated andestrogen receptor independent mechanisms
using human breast cell lines to compare compounds to 17 beta-
estradiol onboth the activation and repression of endogenous genes.
Finally, the applicant will specifically test explanations of
theapparent paradox these compounds exhibit, high biological activity
with low receptor affinity. By exploring thesecompounds and the
apparent paradox they present, increased understanding of the
mechanisms of action of non-steroidalenvironmental estrogens will be
gained. This pilot project will validate these molecular approaches
for definingestrogenic activity, first for our model compounds and, in
the future, for evaluation of other chemicals. All of these goalshave
a direct relationship to the etiology of breast cancer and the actions
of chemicals and hormones.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: HUMAN, IN VITRO
- Keywords for Experimental Endpoints: MOLECULAR, CARCINOGENESIS, HORMONE RECEPTORS
- Chemical Agents: DOISYNOLIC/ALLENOLIC ACIDS
- Performing Institution: WASHINGTON UNIVERSITY
- Contact: CONTRACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21; NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301-496-5515;
LEEE@OD.NCI.NIH.GOV
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