A Role for the Clock Gene <i>Per1</i> in Prostate Cancer

Cao, Qi; Gery, Sigal; Dashti, Azadeh; Ding, Yin; Zhou, Yan; Gu, Jiang; Koeffler, H. Phillip

doi:10.1158/0008-5472.can-08-4199

Cited by 159 publications

(162 citation statements)

References 44 publications

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“…[28][29][30] PER1 and PER2 also interact with the androgen receptor (AR) or estrogen receptor (ER), respectively, in that PER1 inhibits AR-dependent transcription and PER2 induces ER degradation. 31,32) These findings are consistent with the idea that clock proteins act as key players in the cell cycle and DDR by interacting directly with and regulating the functions of the proteins mediating these processes.…”

Section: The Physiological Functions Of Core Circa-dian Regulatorssupporting

confidence: 87%

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Uchida

Hirayama

Nishina

2010

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFrom bacteria to humans, almost all organisms can adapt the timing of their physiology to the cyclic changes of their environment, thanks to a naturally-selected intrinsic timekeeping system called the circadian clock. 1) The circadian clock enhances the physiological efficiency and survival of an organism by organizing its behavior and body functions. 2,3) During the circadian day, the organism's physiology is given over to catabolic processes, whereas the anabolic functions of growth, repair and consolidation occur at night. To achieve this schedule in mammals, the circadian clock regulates a number of physiological functions, including sleep and wakefulness, food intake, body temperature, cardiovascular and renal activity, hormone production, hepatic metabolism and immune responses. 4,5) Accordingly, disruption of the circadian clock in humans has been linked to profound effects on health, including insomnia, stomach ailments, depression and cancer. 4,5) In most organisms, the molecular mechanisms underlying the establishment and maintenance of biological rhythms comprise interconnected transcription-translation feedback loops in which some clock factors repress their own transcription once they have attained critical levels. 2,3) These oscillators have the property of being endogenous and cellautonomous systems that maintain their rhythm in the absence of external time cues. 6) Both vertebrates and invertebrates have circadian oscillators scattered throughout their bodies. 7,8) In mammals, the circadian system is composed of both central and peripheral oscillators. 7) The mammalian central clock is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus of the brain. 9) This central clock acts as a coordinator and provides time signals via both neural and humoral routes that entrain independent peripheral clocks. Dysfunction of the central clock does not inactivate the peripheral clocks but instead causes individual peripheral oscillators to become temporally uncoupled. [10][11][12] To guarantee that an organism's behavior remains tied to the rhythms of its environment, the circadian clock must be able to reset itself in response to environmental cues. 9,13,14) The main environmental stimulus for organisms is light, which is provided in day-night cycles. Mammals have no photoreceptors in peripheral tissues, 15) so that the effect of light on peripheral clocks is indirect. 13) For the mammalian clock, the SCN integrates photic cues from the retina and uses neural and humoral signals to transmit this information to peripheral clocks, synchronizing them. [16][17][18] This communication between the central and peripheral clocks results in the seamless regulation of fundamental physiological functions. 4,8) Interestingly, peripheral clocks can also respond directly to SCN-independent signals such as feeding and temperature change. 19,20) However, the physiological role of SCN-independent responses of peripheral clocks is not yet fully understood. A recent study has reported that ...

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Section: The Physiological Functions Of Core Circa-dian Regulatorssupporting

confidence: 87%

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Uchida

Hirayama

Nishina

2010

Biological & Pharmaceutical Bulletin

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“…In human endometrial carcinoma, loss of per1 protein is commonly observed in tumor cells, but not in the adjacent normal cells (24). A metaanalysis of microarray expression studies showed that Per1 is down-regulated in human prostate cancer as compared with normal prostate tissue (18). CK1ε gene expression was found to be overexpressed in six kinds of cancer tissues as compared with adjacent normal tissues (25).…”

Section: Discussionmentioning

confidence: 99%

“…As for circadian genes, Bmal1 was shown to be a positive regulator of tumor growth and metastasis in cancer (17). Moreover, overexpression of per1 in prostate cancer cells causes significant growth inhibition and apoptosis (18). In addition, per2 plays a key role in tumor suppression, controlled by genes such as c-myc and cyclin D1 through the activity of Bmal1/clock heterodimers (19), and Per2 gene overexpression induces cancer cell apoptosis (20).…”

Section: Introductionmentioning

confidence: 99%

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Oshima

2011

Oncol Rep

102

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Abstract. circadian rhythms are daily oscillations in various biological processes, generated by the feedback loops of eight core circadian genes: Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1 and Casein Kinase I ε (CKIε). recent studies have suggested that circadian genes participate in the growth and development of various cancers. this study examined the relations of circadian gene expression to clinicopathological factors and outcomes in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. the relative expression levels of the circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. expression of the Clock gene and the CKIε gene in cancer tissue were significantly higher compared to that in adjacent normal mucosa. expression of the Per1 and Per3 genes in cancer tissue was significantly lower compared to that in adjacent normal mucosa. Analysis of the relations between clinicopathological features and expression of the eight circadian genes in cancer tissue showed that high expression of the Bmal1 gene and low expression of the Per1 gene correlated with liver metastasis. on analysis of the relations between outcomes and gene expression, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene. overexpression of the Bmal1 gene and reduced expression of the Per1 gene may thus be useful predictors of liver metastasis. Moreover, reduced expression of the Per2 gene may be a predictor of outcomes in patients with colorectal cancer. Introductioncircadian rhythms are daily oscillations in various biologic processes. In mammals, the master circadian pacemaker is located in the suprachiasmatic nuclei (scn) (1). the master circadian clock coordinates peripheral circadian clocks within virtually every cell in the body (2). this coordination is accomplished directly through autonomic nervous system innervation and indirectly through daily rhythmic synthesis and release of an array of hypothalamic, pituitary, and dispersed endocrine hormones (3-6). the molecular mechanism of circadian oscillation in the scn and peripheral cells is based on the feedback loops of eight core circadian genes (3,7,8). these eight genes are Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1, and Casein Kinase I ε (CKIε). the feedback loops of the eight core circadian genes are as follows. the Clock gene remains steady throughout the 24-h day. High levels of Bmal1 promote the formation of Bmal1/clock heterodimers. these heterodimers bind to e-box sequences in the promoters of the Cry and Per genes to activate transcription. Bmal1/clock heterodimers can also inhibit Bmal1 transcription. After transcription and translation, the per proteins accumulate in the cytoplasm and are phosphorylated by...

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“…Similarly, clock-deficient mouse strains (notably Per2-deficient mice) have been documented to have increased spontaneous cancer rates in some, but not all studies (Antoch et al, 2013;Fu et al, 2002). This reflects possible increases in DNA damage and supports a role for clock genes as tumor suppressors (Cao et al, 2009;Yang et al, 2009). However, these observations are a simplification: other clock-deficient mice do not show increased cancer rates (Antoch et al, 2008;Gauger and Sancar, 2005), and cell lines from multiple clock-deficient strains possess normal DNA repair properties (Gaddameedhi et al, 2012).…”

Section: Circadian Control Of Cell Divisionmentioning

confidence: 93%

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

Brown

2014

Development

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A biological 'circadian' clock conveys diurnal regulation upon nearly all aspects of behavior and physiology to optimize them within the framework of the solar day. From digestion to cardiac function and sleep, both cellular and systemic processes show circadian variations that coincide with diurnal need. However, recent research has shown that this same timekeeping mechanism might have been co-opted to optimize other aspects of development and physiology that have no obvious link to the 24 h day. For example, clocks have been suggested to underlie heterogeneity in stem cell populations, to optimize cycles of cell division during wound healing, and to alter immune progenitor differentiation and migration. Here, I review these circadian mechanisms and propose that they could serve as metronomes for a surprising variety of physiologically and medically important functions that far exceed the daily timekeeping roles for which they probably evolved.

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A Role for the Clock Gene Per1 in Prostate Cancer

Cited by 159 publications

References 44 publications

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

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