Alterations in Cell Signaling Pathways in Breast Cancer Cells after Environmental Exposure

Kulp, K ; McCutcheon-Maloney, S M ; Bennett, L M

Lawrence Livermore National Laboratory

关键词: Diseases;    Mammary Glands;    Us Superfund;    Genes;    Cell Proliferation;   

DOI  :  10.2172/15003409
RP-ID  :  UCRL-ID-151397
RP-ID  :  W-7405-ENG-48
RP-ID  :  15003409

美国|英语

来源: UNT Digital Library

【 摘 要 】

Recent human epidemiological studies suggest that up to 75% of human cancers can be attributed to environmental exposures. Understanding the biologic impact of being exposed to a lifetime of complex environmental mixtures that may not be fully characterized is currently a major challenge. Functional endpoints may be used to assess the gross health consequences of complex mixture exposures from groundwater contamination, superfund sites, biologic releases, or nutritional sources. Such endpoints include the stimulation of cell growth or the induction of a response in an animal model. An environmental exposure that upsets normal cell growth regulation may have important ramifications for cancer development. Stimulating cell growth may alter an individual's cancer risk by changing the expression of genes and proteins that have a role in growth regulatory pathways within cells. Modulating the regulation of these genes and their products may contribute to the initiation, promotion or progression of disease in response to environmental exposure. We are investigating diet-related compounds that induce cell proliferation in breast cancer cell lines. These compounds, PhIP, Flor-Essence{reg_sign} and Essiac{reg_sign}, may be part of an everyday diet. PhIP is a naturally occurring mutagen that is formed in well-cooked muscle meats. PhIP consistently causes dose-dependent breast tumor formation in rats and consumption of well-done meat has been linked to increased risk of breast cancer in women. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics are complementary and alternative medicines used by women who have been diagnosed with breast cancer as an alternative therapy for disease treatment and prevention. The long-term goal of this work is to identify those cellular pathways that are altered by a chemical or biologic environmental exposure and understand how those changes correlate with and or predict changes in human health risk. This project addressed this goal by measuring alterations in cell growth pathways in the human MCF-7 breast cancer cell line using functional cell proliferation and reporter assays in combination with new macroarray technology after exposure to PhIP and the herbal tonics.