Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice

Hua, Hui; Wang, Y; Wan, Chaomin; Liu, Y; Zhu, Bin; Wang, X; Wang, Z; Ding, Jian

doi:10.1038/sj.cgt.7701061

Cited by 61 publications

(52 citation statements)

References 13 publications

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“…overexpression of the Per2 gene induces cancer cell apoptosis (20), and inhibits the neoplastic growth of cancer cells (30). Moreover, Per2 gene mutations have been identified in human colorectal and breast cancers (31), and overexpression of per2 inhibits tumor proliferation in culture as well as in animals (32,33). In our study, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene.…”

Section: Discussionsupporting

confidence: 60%

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

Oshima

2011

Oncol Rep

100

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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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Section: Discussionsupporting

confidence: 60%

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

Oshima

2011

Oncol Rep

100

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“…However, no such effect was found for NIH-3T3 cells (Hua et al 2006). Furthermore, intratumoral Per2 gene delivery significantly slowed down the growth of LLC transplanted in mice through inhibition of proliferating cell nuclear antigen (PCNA) expression and apoptosis induction (Hua et al 2007).…”

Section: Interactions Between Molecular Clock and Cellular Proliferationmentioning

confidence: 98%

“…The increased proliferation and decreased apoptosis that are associated with clock disruption in tumors can be reverted through overexpressing Per1 or Per2 in malignant cells (Gery et al 2006;Hua et al 2006Hua et al , 2007. Thus, overexpression of Per1-sensitized human cancer cells to lowdose radiation that produced DNA-damage-induced apoptosis, whereas inhibition of Per1 cells blunted apoptosis in these tumor cells (Gery et al 2006).…”

Section: Interactions Between Molecular Clock and Cellular Proliferationmentioning

confidence: 98%

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Lévi

Filipski²,

Iurisci³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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“…The age of the patient ranged from 17 to 69 with a mean of 39.4 years, with 38 men and 31 women. The tissues were frozen or formalinfixed immediately after surgical resection and stored in liquid nitrogen as Hui et al previously described (Hua et al, 2007). The glioma tissue and tumor free specimens were surgically obtained between 11:00 and 15:00.…”

Section: Patientsmentioning

confidence: 99%

“…The encoded proteins, which associate in multimeric complexes, engage in a negative feedback loop to repress transactivation by CLOCK/BMAL1 in the nucleus. The expression of these clock genes and their rhythmic regulation are not unique to the SCN but,instead, are widely distributed in many cells and tissues (Morse et al, 2002) and it is well-known that the alterations in circadian rhythm can be a risk factor for the development of cancers in both animal and human tumors (Metz et al, 2005;Yeh et al, 2005;Hua et al, 2007;Huttmann et al, 2012), including breast tumors, human endometrial carcinoma (Huttmann et al, 2012), Lewis lung carcinoma and lymphocytic leukemia (Yeh et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Deregulated Expression of Cry1 and Cry2 in Human Gliomas

Luo¹,

Fan²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.

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Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice

Cited by 61 publications

References 13 publications

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

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

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Deregulated Expression of Cry1 and Cry2 in Human Gliomas

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