Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylation of the cytoskeletal filament protein, cytokeratin-8, along with thiol arylation of H3 nuclear histones. Exogenous or endogenous quinones can also induce ligand-independent nuclear translocation and phosphorylation of ER; with excess exposure, these quinones can arylate ER zinc fingers, impairing ER DNA-binding and altering ER-inducible gene expression. Immunoaffinity enrichment for low abundance proteins such as ER, coupled with modern mass spectrometry techniques, promises to improve understanding of the protein-modifications produced by endogenous and exogenous quinone exposure and their role in the development or progression of epithelial malignancies such as breast cancer.
Novel pathways associated with quinone-induced stress in breast cancer cells. Publishing Authors By Initials
