Novel pathways associated with quinone-induced stress in breast cancer cells
Novel pathways associated with quinone-induced stress in breast cancer cells
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DOI：
10.1080/03602530600959391
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发表时间：
2006-01-01
影响因子：
5.9
通讯作者：
Scott, Gary K.
中科院分区：
文献类型：
--
作者：
Benz, Christopher C.;Atsriku, Christian;Scott, Gary K.
过表达配体结合核转录因子雌激素受体（ER）的激素依赖性乳腺癌代表了最常见的乳腺上皮恶性肿瘤形式。乳腺上皮细胞暴露于氧化还原循环和芳基化醌诱导细胞骨架丝蛋白、细胞角蛋白-8的丝裂原活化蛋白激酶磷酸化，沿着H3核组蛋白的巯基芳基化。外源性或内源性醌类也可以诱导不依赖配体的核转位和ER的磷酸化;过量暴露，这些醌类可以使ER锌指芳基化，损害ER DNA结合并改变ER诱导的基因表达。免疫亲和富集低丰度蛋白质，如ER，再加上现代质谱技术，有望提高内源性和外源性醌暴露产生的蛋白质修饰及其在上皮恶性肿瘤，如乳腺癌的发展或进展中的作用的理解。
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.