title: Novel pathways associated with quinone-induced stress in breast cancer cells.
abstract: 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.
authors.affiliation: Cancer and Developmental Therapeutics Program, Buck Institute for Age Research, Novato, CA 94945, USA. cbenz@buckinstitute.org
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Benz
authors.forename: Christian
authors.initials: C
authors.lastname: Atsriku
authors.forename: Christina
authors.initials: C
authors.lastname: Yau
authors.forename: David
authors.initials: D
authors.lastname: Britton
authors.forename: Birgit
authors.initials: B
authors.lastname: Schilling
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Gibson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Baldwin
authors.forename: Gary K
authors.initials: GK
authors.lastname: Scott
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004273:DNA, Neoplasm; D011809:Quinones