Effects of light and food schedules on liver and tumor molecular clocks in mice.

Effects of light and food schedules on liver and tumor molecular clocks in mice. Research Abstract Details 

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Effects of light and food schedules on liver and tumor molecular clocks in mice. Abstract Text:

Elisabeth Filipski,Pasquale F Innominato,MingWei Wu,Xiao-Mei Li,Stefano Iacobelli,Li-Jian Xian,Francis ,

BACKGROUND: Disrupted circadian coordination accelerates malignant growth, but the molecular mechanism is unclear. METHODS: Healthy or Glasgow osteosarcoma-bearing mice (n = 162) were synchronized with light and darkness over 2-3 weeks, submitted to an 8-hour advance onset of light every 2 days (chronic jet lag) to disrupt circadian coordination, or submitted to chronic jet lag and meal timing to prevent molecular clock alteration. The expression of molecular clock genes and of the cell cycle genes c-Myc and p53 in liver and tumor was determined with quantitative reverse transcription-polymerase chain reaction at six circadian times over a 24-hour period of light and darkness and analyzed with analysis of variance and cosinor. Tumor weight was measured daily over the course of the experiment. All statistical tests were two-sided. RESULTS: In synchronized mice, mean mRNA levels of clock genes Rev-erbalpha, Per2, and Bmal1 varied by 206-, four-, and 26-fold, respectively, over the 24 hours in healthy mouse liver; by 36-, 35-, and 32-fold in the livers of tumor-bearing mice; and by 9.4-, 5.5-, and sixfold in tumor tissue (P = .046 to <.001). In mice subjected to chronic jet lag, the periodic changes were dampened and the clock gene rhythms were temporally shifted in liver and ablated in tumor, and tumor growth was accelerated. Meal timing reversed the chronic jet lag-induced alterations in Rev-erbalpha and Per2 expression in liver and of all three clock genes in tumor and slowed tumor growth. Tumor growth differed as a function of light and feeding schedules (P = .04). No obvious rhythm was detected for p53 or c-Myc in liver or tumor tissues of synchronized mice. In healthy mice subjected to chronic jet lag, the mean level of p53 expression was cut in half (P = .002), and a 12-fold circadian variation in c-Myc mRNA level (P = .03) was induced in the liver of healthy mice, whereas complex expression patterns were found in the liver and tumor of tumor-bearing mice. CONCLUSIONS: Altered light-dark or feeding schedules modified the expression of molecular clock genes and genes involved in carcinogenesis and tumor progression.

Effects of light and food schedules on liver and tumor molecular clocks in mice. Publishing Authors By Initials

E Filipski,PF Innominato,M Wu,XM Li,S Iacobelli,LJ Xian,F ,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

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Effects of light and food schedules on liver and tumor molecular clocks in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the National Cancer Institute

VOLUME: 97

Page Numbers: 507-17

Journal Abbreviation: J. Natl. Cancer Inst.

ISSN: 1460-2105

DAY: 6

MONTH: Apr

YEAR: 2005

Effects of light and food schedules on liver and tumor molecular clocks in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503089

Effects of light and food schedules on liver and tumor molecular clocks in mice. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: metabolism

Chemical & Substance for Abstract: Effects of light and food schedules on liver and tumor molecular clocks in mice. Information

Substance Name: Tumor Suppressor Protein p53

Registry Number: 0

Grant and Affiliation Information for Effects of light and food schedules on liver and tumor molecular clocks in mice.

AFFILIATION: INSERM E 0354 Chronothérapeutique des cancers, Hôpital P. Brousse and Université Paris XI, 94807 Villejuif Cedex, France.

Country: United States

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MEDLINETA: J Natl Cancer Inst

REFSOURCE: J Natl Cancer Inst. 2005 May 18;97(10):7

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