The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA-Damage Response In Vivo

Fu, Loning; Pélicano, Hélène; Liu, Jinsong; Huang, Peng; Lee, Cheng‐Chi

doi:10.1016/s0092-8674(02)01223-0

Cited by 420 publications

(676 citation statements)

References 0 publications

Supporting

Mentioning

638

Contrasting

Unclassified

Order By: Relevance

“…As the Per2 gene is regulated by Clock, it is possible that the expression of this protein might be involved in DNA damage-induced apoptosis. The analysis of the expression profile showed that several DNA damage-inducible genes such as members of the growth-arrest and DNA damage (GADD) family that block cell-cycle progression (Liebermann and Hoffman, 2002) and cyclin genes were controlled by circadian regulators (Fu et al, 2002). Taken together, these results indicate that the cell cycle-regulating mechanism in cisplatin-resistant cells is regulated by Clock.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines

et al. 2007

View full text Add to dashboard Cite

The mechanisms underlying cellular drug resistance have been extensively studied, but little is known about its regulation. We have previously reported that activating transcription factor 4 (ATF4) is upregulated in cisplatinresistant cells and plays a role in cisplatin resistance. Here, we find out a novel relationship between the circadian transcription factor Clock and drug resistance. Clock drives the periodical expression of many genes that regulate hormone release, cell division, sleep-awake cycle and tumor growth. We demonstrate that ATF4 is a direct target of Clock, and that Clock is overexpressed in cisplatin-resistant cells. Furthermore, Clock expression significantly correlates with cisplatin sensitivity, and that the downregulation of either Clock or ATF4 confers sensitivity of A549 cells to cisplatin and etoposide. Notably, ATF4-overexpressing cells show multidrug resistance and marked elevation of intracellular glutathione. The microarray study reveals that genes for glutathione metabolism are generally downregulated by the knockdown of ATF4 expression. These results suggest that the Clock and ATF4 transcription system might play an important role in multidrug resistance through glutathione-dependent redox system, and also indicate that physiological potentials of Clock-controlled redox system might be important to better understand the oxidative stress-associated disorders including cancer and systemic chronotherapy.

show abstract

Section: Discussionmentioning

confidence: 91%

“…It has been shown that the Per2-mutant mouse demonstrates increased sensitivity to g-radiation (Fu et al, 2002). As the Per2 gene is regulated by Clock, it is possible that the expression of this protein might be involved in DNA damage-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines

et al. 2007

View full text Add to dashboard Cite

show abstract

“…For example, Clock/Clock mutant mice develop metabolic syndrome and obesity [64], animals with a targeted disruption of the CLOCK transcriptional partner, BMAL1 (Bmal1 −/− knockout mice) display phenotype of premature aging [65], whereas an increase in carcinogenesis has been reported specifically for Per2 mutants [66]. These examples lead to several important conclusions.…”

Section: Non-circadian Function Of Circadian Proteinsmentioning

confidence: 99%

Pharmacological modulators of the circadian clock as potential therapeutic drugs

Antoch

Chernov

2009

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

Circadian clocks are molecular time-keeping systems that underlie daily fluctuations in multiple physiological and biochemical processes. It is well recognized now that dysfunctions of the circadian system (both genetically and environmentally induced) are associated with the development of various pathological conditions. Here we describe the application of high throughput screening approach designed to search for small molecules capable of pharmacological modulation of the molecular clock. We provide evidence for the feasibility and value of this approach for both scientific and therapeutic purposes.

show abstract

“…Per2 mutant mice show increased susceptibility to tumor development, suggesting that Per2 is a tumor suppressor gene (Fu et al, 2002). Expression of Per2 dramatically reduced the growth of MCF-7 cells on plastic and the ability of the cells to form colonies on soft agar (Figures 4a and b).…”

mentioning

confidence: 99%

“…The central clock, through neural, hormonal and metabolic signals, synchronizes the peripheral oscillators, which in turn drive the expression of downstream clock-controlled genes in a tissue-specific manner (Panda et al, 2002;Storch et al, 2002;Miller et al, 2007). Consequently in various tissues, circadian rhythms impinge upon many physiological processes and pathological conditions, including cancer (Fu et al, 2002;Matsuo et al, 2003;Lowrey and Takahashi, 2004;Ko and Takahashi, 2006). Recent studies suggested that circadian disruption is associated with breast tumorigenesis (Hansen, 2001;Chen et al, 2005).…”

mentioning

confidence: 99%

The clock gene Per2 links the circadian system to the estrogen receptor

et al. 2007

View full text Add to dashboard Cite

The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA-Damage Response In Vivo

Cited by 420 publications

References 0 publications

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines

Pharmacological modulators of the circadian clock as potential therapeutic drugs

The clock gene Per2 links the circadian system to the estrogen receptor

Contact Info

Product

Resources

About