The Effect of an Environmental Chemical Receptor on Breast Cancer Stem Cell Development, Function and MaintenanceEPA Grant Number: F13D10719
Title: The Effect of an Environmental Chemical Receptor on Breast Cancer Stem Cell Development, Function and Maintenance
Investigators: Stanford, Elizabeth Ann
Institution: Boston University
EPA Project Officer: Lee, Sonja
Project Period: September 1, 2014 through September 1, 2016
Project Amount: $84,000
RFA: STAR Graduate Fellowships (2013) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Fellowship - Biochemistry
Objective:Recent studies suggest a role for AHR activation by environmental chemicals in breast cancer initiation and invasion. The AHR also is a known regulator of various stem cell lineages, suggesting a possible role for the AHR in generating chemotherapy- resistant, metastatic cancer stem cells. The mechanisms through which the AHR effects these outcomes are unknown. This research will focus on defining the functional relevance of AHR activation by environmental chemicals to breast cancer stem cell (BCSC) development and function.
Approach:Although representing only a small percentage of the whole tumor, BCSCs are believed to be extremely resistant to chemotherapeutics and, thereby, to be responsible for the recurrence and lethal spread of cancer cells after treatment. Preliminary data indicate that activation of the AHR by various environmental chemicals contributes to the development and/or maintenance of BCSCs. This research will compare the ability of a series of environmental AHR activators, including environmental pollutants found to be associated with breast cancer risk in populationbased, epidemiological studies, to increase the number of BCSC-like cells and to drive the emergence of more aggressive, drug-resistant cells. Subsequently, a “snapshot” will be developed of the genetic changes occurring after human breast cancer cells are exposed to environmental AHR stimulators, to map out the genetic mechanisms through which these chemicals influence BCSC development and/or survival.
Based on preliminary findings from a variety of assays evaluating the effect of environmental AHR activators on human cancer cells, it is highly likely that the AHR is controlling the breast cancer stem cell population. These results will help create an invaluable platform for studying AHR signaling in a unique and critical cancer cell subset. Breast cancer stem cells are resistant to chemotherapeutics and responsible for metastasis formation, the cause of death in the majority of breast cancer patients. Collectively, these data will determine the extent to which environmental AHR ligands influence nominal signaling pathways in breast cancer stem cells, helping to elucidate the impact of chemical exposures on cancer malignancy.
Potential to Further Environmental/Human Health Protection
Understanding the contribution of the AHR to development and/or maintenance of breast cancer stem cells will increase understanding of the basic molecular biology of this important cancer cell subset and will help assess the likelihood that environmental chemicals play a role in BCSC development and/or survival. This work represents an important next step in building the argument toward breast cancer prevention through elimination of environmental AHR activators