Journal
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1815, Issue 1, Pages 115-133Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbcan.2010.10.005
Keywords
ROS; Estrogen; Signal transduction; Breast cancer
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Elevated lifetime estrogen exposure is a major risk factor for breast cancer. Recent advances in the understanding of breast carcinogenesis clearly indicate that induction of estrogen receptor (ER) mediated signaling is not sufficient for the development of breast cancer. The underlying mechanisms of breast susceptibility to estrogen's carcinogenic effect remain elusive. Physiologically achievable concentrations of estrogen or estrogen metabolites have been shown to generate reactive oxygen species (ROS). Recent data implicated that these ROS induced DNA synthesis, increased phosphorylation of kinases, and activated transcription factors, e.g., AP-1, NRF1, E2F, NF-kappa B and CREB of non-genomic pathways which are responsive to both oxidants and estrogen. Estrogen-induced ROS by increasing genomic instability and by transducing signal through influencing redox sensitive transcription factors play important role (s) in cell transformation, cell cycle, migration and invasion of the breast cancer. The present review discusses emerging data in support of the role of estrogen induced ROS-mediated signaling pathways which may contribute in the development of breast cancer. It is envisioned that estrogen induced ROS mediated signaling is a key complementary mechanism that drives the carcinogenesis process. ROS mediated signaling however occurs in the context of other estrogen induced processes such as ER-mediated signaling and estrogen reactive metabolite-associated genotoxicity. Importantly, estrogen-induced ROS can function as independent reversible modifiers of phosphatases and activate kinases to trigger the transcription factors of downstream target genes which participate in cancer progression. (C) 2010 Elsevier B.V. All rights reserved.
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