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Author (up) Dauchy, R.T.; Xiang, S.; Mao, L.; Brimer, S.; Wren, M.A.; Yuan, L.; Anbalagan, M.; Hauch, A.; Frasch, T.; Rowan, B.G.; Blask, D.E.; Hill, S.M. url  doi
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  Title Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer Type Journal Article
  Year 2014 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume 74 Issue 15 Pages 4099-4110  
  Keywords *Cancer; breast cancer; melatonin; endocrinology; tamoxifen; *Circadian Rhythm; circadian disruption; human health; epidemiology  
  Abstract Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERalpha(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. Cancer Res; 74(15); 4099-110. (c)2014 AACR.  
  Address Departments of Structural and Cellular Biology and Tulane Cancer Center and Louisiana Cancer Research Consortium; Tulane Circadian Cancer Biology Group; and  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:25062775; PMCID:PMC4119539 Approved no  
  Call Number IDA @ john @ Serial 355  
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