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Author Filipski, E.; Li, X.M.; Levi, F.
Title Disruption of circadian coordination and malignant growth Type Journal Article
Year 2006 Publication (up) Cancer Causes & Control : CCC Abbreviated Journal Cancer Causes Control
Volume 17 Issue 4 Pages 509-514
Keywords Human Health; Animals; Biological Clocks; Body Temperature; Cell Cycle Proteins; Cell Line, Tumor; Chronobiology Disorders/*complications/physiopathology; Circadian Rhythm; Corticosterone/blood; DNA-Binding Proteins/metabolism; Jet Lag Syndrome/complications/physiopathology; Lymphocyte Count; Mice; Neoplasm Transplantation; Nuclear Proteins/metabolism; Nuclear Receptor Subfamily 1, Group D, Member 1; Osteosarcoma/*pathology/physiopathology; Pancreatic Neoplasms/*pathology/physiopathology; Period Circadian Proteins; Receptors, Cytoplasmic and Nuclear/metabolism; Suprachiasmatic Nucleus/physiopathology; Transcription Factors/metabolism
Abstract Altered circadian rhythms predicted for poor survival in patients with metastatic colorectal or breast cancer. An increased incidence of cancers has been reported in flying attendants and in women working predominantly at night. To explore the contribution of circadian structure to tumor growth we ablated the 24-h rest-activity cycle and markedly altered the rhythms in body temperature, serum corticosterone and lymphocyte count in mice by complete stereotaxic destruction of the suprachiasmatic nuclei (SCN) or by subjecting the mice to experimental chronic jet-lag. Such disruption of circadian coordination significantly accelerated malignant growth in two transplantable tumor models, Glasgow osteosarcoma and Pancreatic adenocarcinoma. The mRNA expression of clock genes per2 and reverb-alpha in controls displayed significant circadian rhythms in the liver (Cosinor, p=0.006 and p=0.003, respectively) and in the tumor (p=0.04 and p<0.001, respectively). Both rhythms were suppressed in the liver and in the tumor of jet lagged mice. This functional disturbance of molecular clock resulted in down regulation of p53 and overexpression of c-Myc, two effects which may favor cancer growth. CONCLUSIONS: These results indicate that circadian system could play an important role in malignant growth control. This should be taken into consideration in cancer prevention and therapy.
Address INSERM E 354 Cancer Chronotherapeutics, Hopital Paul Brousse, Villejuif, France. filipski@vjf.inserm.fr
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 0957-5243 ISBN Medium
Area Expedition Conference
Notes PMID:16596304 Approved no
Call Number LoNNe @ kagoburian @ Serial 748
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