Disruption of Endocrine Pathways by Environmental Arsenic and Development of Estrogen Receptor-Negative Breast Cancer
Catherine Propper, PhD Professor, Department of Biological Sciences, College of Engineering, Forestry, & Natural Sciences
Donato Romagnolo, PhD Professor, Department of Nutritional Sciences and College of Agriculture and Life Sciences
Many chemicals released into the environment, either through human activities or natural geological processes, affect the function of human beings. Arsenic is a common chemical naturally found in ground and surface waters, and exposure to arsenic through drinking water can induce shifts in natural physiological function. In some parts of the globe, levels of arsenic are so high that ingestion through food or water is enough to cause severe toxic effects. In other parts of the world, such as in Arizona, arsenic levels in water resources are above the Environmental Protection Agency’s recommended limits. These levels of arsenic exposure, while not high enough to be highly toxic, are sufficient to interact with natural chemicals in the bloodstream called hormones that are important to maintaining normal function of cells and tissues.
Estrogen is a natural hormone important in normal breast function, but also has effects on breast cancer outcomes. Many cancers are sensitive to estrogen (termed estrogen receptor positive breast cancers). Treatment of these cancers relies on many drug therapies including some that block the ability of estrogen to increase the size and number of tumors. Recent evidence suggests that arsenic acts as a disrupter of estrogen action and may affect changes in estrogen processes that could shift the effectiveness of these drug therapies. Therefore, arsenic exposure may affect the treatability of the tumors.
While breast cancer incidence rates in Arizona Native American populations does not differ from non-native populations, breast cancer still remains the most deadly cancer for Navajo and Tohono O’odham women in Arizona. Furthermore, the mortality rate for this disease is above that of non-native populations. The reasons for this difference in survivorship are not well defined, but potential explanations include differences in screening rates, access to treatment, and differences in response to drug therapies. Early evidence in our laboratories and others indicate that arsenic affects estrogen-based processes, suggesting that arsenic exposure could play a role in the progression of estrogen sensitive breast cancers. This project will investigate whether arsenic affects estrogen biology such that exposure interacts with a common drug therapy used in the treatment of estrogen responsive cancers. Specifically, we will use three research models for breast cancer, zebrafish, mice and tissue cell lines, to determine whether arsenic affects estrogen-like processes associated with breast cancer and one of its chemotherapeutic options.
Our project advances the overall goals of the NACP by developing cancer research in Dr. Propper’s laboratory with the expertise of Dr. Romagnolo’s background in cancer biology. We will honor the culture of the Native American communities we serve by collaborating with water managers and human health personnel to formulate appropriate arsenic education programs in local communities. Last, we will increase the number of Native American students trained in cancer research and health care policy.