The Role of Circadian Regulation in Cancer

Gery, Sigal; Koeffler, H. Phillip

doi:10.1101/sqb.2007.72.004

Cited by 67 publications

(60 citation statements)

References 54 publications

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“…One possible explanation is that the HepG 2 we used here is a cancer cell line and in many cancers the circadian clock systems are disrupted and the expression of the circadian clock genes does not exhibit regular rhythmicity any more. 27 However, our purpose in this experiment was to assess the impact of BAF60a abolishment on the expression of circadian clock (although not the normal circadian clock) and our results indeed showed that BAF60a is essential for the maintenance of circadian gene expression.…”

Section: Baf60a Is Rhythmically Expressed In Mousementioning

confidence: 83%

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

et al. 2011

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Many aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism, are under precise control by the mammalian circadian clock. However, the molecular mechanism for coordinate integration of the circadian clock and various metabolic pathways is poorly understood. Here we show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show abnormalities in the rhythmic expression pattern of clock and metabolic genes and in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs the oscillation of clock genes in serum-shocked HepG 2 cells. At the molecular level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation of retinoid-related orphan receptor alpha (RORa). In addition, BAF60a is present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into the active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinated regulation of hepatic circadian clock and energy metabolism in mammals. (HEPATOLOGY 2011;54:1410-1420 M any physiological events in mammals, including locomotor activity, sleep, blood pressure, circulating hormones, and energy metabolism show diurnal fluctuation. 1,2 These intrinsic biological rhythms are mainly entrained by light-dark (LD) and feeding cycles. The mammalian master clock resides in the hypothalamic suprachiasmatic nucleus (SCN) and drives slave oscillators distributed in various peripheral tissues through behavioral and neuroendocrine signals. However, Damiola et al. 3 found that peripheral oscillators can be uncoupled and reset from the central pacemaker by restricted feeding. Their findings are supported by the subsequent report showing that restricted feeding entrains the circadian rhythms in peripheral tissues, dominantly in the liver, but leaving SCN rhythms unaffected. 4 Also, both food availability and the temporal pattern of feeding determine the repertoire, phase, and amplitude of the circadian transcriptome in mouse liver. 5 All these studies indicate that nutritional signals play a dominant role in the regulation of peripheral clock function. At the molecular level, Clock and Bmal1 are two basic helix-loop-helix transcription factors that activate the transcription of period (Per) and cryptochrome (Cry) genes. 6 Per and Cry proteins in turn inhibit their own expression by repressing Clock/Bmal1 activity, forming the critical feedback loop within the clock circuitry. In addition, the orphan nuclear receptors of the ROR and Rev-erb families are also implicated in the control of circadian clock function. 7,8 Abbreviations: ChIP, chromatin immunoprecipitation; CO, carbon monoxide; CoIP, coimmunoprecipitation; GFP, green fluorescent protein; GR, glucocorticoid receptor; H3K4me3, trimethylation of lysine 4 of histone 3; H3K9me2, dimethylation of lysine 9 of histone 3; HAT, histone acetyltransferase; HDAC, histone deacetyla...

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Section: Baf60a Is Rhythmically Expressed In Mousementioning

confidence: 83%

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

et al. 2011

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“…15,16 The possible functions of PER3 in tumor development have not been explored, but links to breast cancer are supported by biochemical studies demonstrating the existence of complexes, including proteins of the PER family together with the estrogen receptor (ER), 17,18 and by reports of association between a polymorphism in the human PER3 gene and breast cancer susceptibility. 19 The location of the PER3 gene within a region that is commonly deleted in breast cancers suggested a possible link to epidemiologic studies 20,21 showing an association between disrupted sleep cycles and higher risk of developing breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Second, previous data from clinical trials of chronotherapy suggest that the timing of cancer treatment during the day may affect individual patient responses. 45,46 Elucidation of the relationship between control of sleep homeostasis and circadian rhythms, PER gene expression, and DNA damage responses may help in understanding the epidemiologic data linking sleep disruption to breast cancer susceptibility, 17,20,21 but further detailed studies will be required to elucidate the exact mechanisms involved. Finally, small-molecule drugs that help to restore the balance of the biologic clock in individuals with frequent sleep disruption may have potential as chemopreventive agents for breast and some other cancer types.…”

Section: 37mentioning

confidence: 99%

“…Although the specific molecular mechanisms remain to be elucidated, increasing evidence points to a role for circadian rhythm genes in cell cycle control and DNA damage responses 11,43 as well as in hormonal control of gene expression. 17,18 PER2 has been identified as an estrogen-inducible ER corepressor that forms heterodimers with PER3 to enter the nucleus. Deletion of PER3 prevents nuclear import and, instead, promotes accumulation of PER2 in the cytoplasm.…”

Section: 37mentioning

confidence: 99%

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Deletion of thePER3Gene on Chromosome 1p36 in Recurrent ER-Positive Breast Cancer

Climent

Pérez-Losada

Quigley

et al. 2010

JCO

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Purpose To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development. Patients and Methods The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node–negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer. Results Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) – positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2. Conclusion Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.

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“…Now, biological 24-hour rhythms allow organisms, including humans, to tune physiology to daily cycles of sunlight and darkness, of day and night. That proper circadian regulation is essential for the well-being of organisms is beyond doubt (2). Importantly, central timing and an appropriate coordination of circadian rhythms is Erren et al achieved by a circadian master clock in the brain, which collectively sets or governs-similar to Greenwich mean time, which provides the reference time, independent of the geographic location, for billions of other clocks in the world-a plethora of peripheral clocks.…”

mentioning

confidence: 99%

Shift work, chronodisruption and cancer?—the IARC 2007 challenge for research and prevention and 10 theses from the Cologne Colloquium 2008

Erren

Morfeld²,

Stork³

et al. 2009

Scand J Work Environ Health

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The Role of Circadian Regulation in Cancer

Cited by 67 publications

References 54 publications

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

Deletion of thePER3Gene on Chromosome 1p36 in Recurrent ER-Positive Breast Cancer

Shift work, chronodisruption and cancer?—the IARC 2007 challenge for research and prevention and 10 theses from the Cologne Colloquium 2008

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