Biologically relevant screening of endocrine disruptors
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical overview of the research topic and relevance to breast cancer:
 
 
 
 Endocrine disruptors are environmental chemicals that interfere with the action and formation of steroid hormones in the body. Estrogen, an important steroid hormone, is known to play key roles in hormone dependent breast cancer. Although extensive efforts have been made by many outstanding researchers worldwide, a definitive conclusion regarding the impact of such chemicals in breast cancer has not been established. The goal of this proposed research is to develop screening assays for identifying and testing chemicals with relevance to known and suspected causes of estrogen-dependent breast cancer.
 
 
 
 
 
 Research questions:
 
 
 
 60% of premenopausal and 75% of postmenopausal patients have estrogen-dependent breast cancer. Estrogen receptor (ER) and aromatase are key players in this type of breast cancer. In our body, estrogen promotes breast cancer through its interaction with a receptor protein, estrogen receptor (ER) and drives the expression of growth factors that stimulate the growth of breast tumors. Aromatase is a protein that makes estrogen. In addition, ERR? is a receptor with similar activity as ER, but it can function without estrogen. Findings from this and other laboratories allow us to hypothesize that environmental chemicals will play critical roles in modulating breast cancer through these three proteins. We will develop functionally relevant assays that allow the identification of environmental chemicals contributing to breast cancer.
 
 
 
 
 
 General methodology:
 
 
 
 (1) We will refine a breast cancer-relevant high-throughput screening assay using a breast cancer cell line generated in our laboratory that is positive for all three important targets (ER, aromatase and ERR?) of endocrine disruptors. (2) A set of breast cancer-relevant genes will be tested for usage as markers to confirm the physiological importance of the chemicals identified from the screening assay. (3) Experiments will be performed to identify additional novel markers for environmental chemical-mediated responses in breast cancer. (4) Animal experiments will be performed to confirm the utility of the screening cell line and gene expression signature in the prediction of the effects of endocrine disruptors in our body.
 
 
 
 
 
 Innovative elements:
 
 
 
 A team of investigators with research experience in breast cancer translational research, estrogen biology, bioinformatics analysis, and animal experiments has been assembled at our institution to develop novel and breast cancer-relevant assays for an endocrine disruptor screen. New and potentially useful cell line and gene expression signatures will be established to be important tools to identify environmental chemicals with the potential to promote hormone-dependent breast cancer. An important collaboration with Dr. C. Teng, a scientist who is involved in the Tox21 project (a federal effort for environmental chemical screen) has been established. She will evaluate our assays in a timely manner through the Tox21 assay program at the National Toxicology Program, National Institute of Environmental Health Sciences. Collaboration between scientists at City of Hope and those at Tox21 community will facilitate the development of innovative assays to identify chemicals that can contribute to breast cancer.
 
 
 
 
 
 Advocacy involvement:
 
 
 
 Information about the risk of endocrine disruptors to breast cancer are often conflicting and confusing to patients and advocates. The development of breast cancer-relevant assays to help identify such environmental chemicals would be of great interest and receive support from patients and patient groups. Dr. Sandra Finestone, a member of Breast Cancer Solutions and the Executive Director of Hope Wellness Center, will serve as the advocate of this project, in the design of the laboratory studies and communicate the findings and progress of the project.