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Author deHaro, D.; Kines, K.J.; Sokolowski, M.; Dauchy, R.T.; Streva, V.A.; Hill, S.M.; Hanifin, J.P.; Brainard, G.C.; Blask, D.E.; Belancio, V.P.
Title Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night Type Journal Article
Year 2014 Publication Nucleic Acids Research Abbreviated Journal Nucleic Acids Res
Volume 42 Issue 12 Pages 7694-7707
Keywords Human Health
Abstract Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue-isolated xenografts of human cancer. Supplementation of human blood with exogenous melatonin or melatonin receptor antagonist during the in situ perfusion establishes a receptor-mediated action of melatonin on L1 expression. Combined tissue culture and in vivo data support that environmental light exposure of the host regulates expression of L1 elements in tumors. Our data imply that light-induced suppression of melatonin production in shift workers may increase L1-induced genomic instability in their genomes and suggest a possible connection between L1 activity and increased incidence of cancer associated with circadian disruption.
Address Department of Structural and Cellular Biology, Tulane School of Medicine, Tulane Cancer Center, New Orleans, LA 70115, USA Tulane Center for Aging, New Orleans, LA 70112, USA vperepe@tulane.edu
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 0305-1048 ISBN (up) Medium
Area Expedition Conference
Notes PMID:24914052; PMCID:PMC4081101 Approved no
Call Number LoNNe @ kyba @ Serial 1414
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