Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-24T08:03:04.770Z Has data issue: false hasContentIssue false

Deregulated Expression of the Per1 and Per2 in Human Gliomas

Published online by Cambridge University Press:  02 December 2014

He-chun Xia*
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Zhan-feng Niu
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Hui Ma
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Shuan-zhu Cao
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Shao-cai Hao
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Zhong-tao Liu
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
Fan Wang
Affiliation:
Department of Neurosurgery, Affiliated Hospital of Ningxia Medical University, Yinchuan, China
*
Department of Neurosurgery in the Affiliated Hospital of Ningxia Medical University, Yinchuan, 75004, China.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

Growing evidence shows that the deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored.

Methods:

Using reverse transcription polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, Per1 and Per2, in 33 gliomas.

Results:

In this study, out of 33 gliomas, 28 were Per1-positive, and 23 were Per2-positive. The expression levels of Per1 and Per2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of Per1 and Per2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was insignificant (P>0.05). While there was no difference in the intensity of immunoactivity for Per2 between high-grade gliomas and low-grade gliomas (r=-0.330, P=0.061), the expression level of Per1 in highgrade gliomas was significantly lower than that in low-grade gliomas(r=-0.433, P=0.012).

Conclusions:

In this study, we found that the expression of Per1 and Per2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in Per1 and Per2 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.

Type
Original Article
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. Gromeier, M, Wimmer, E. Viruses for the treatment of malignant glioma. Curr Opin Mol Ther. 2001; 3 (5): 5038.Google ScholarPubMed
2. Rainov, N, Ren, H. Gene therapy for human malignant brain tumors. Cancer J. 2003; 9 (3): 1808.CrossRefGoogle ScholarPubMed
3. Aschhoff, B. Retrospective study of Ukraine treatment in 203 patients with advanced-stage tumors. Drugs Exp Clin Res. 2000; 26 (5-6): 24952.Google Scholar
4. Sun, JY, Yang, H, Miao, S, Li, JP, Wang, SW, Zhu, MZ, et al. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo. J Phymed. 2009; 16 (11): 10704.Google ScholarPubMed
5. Stummer, W. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006; 7 (5): 392401.CrossRefGoogle ScholarPubMed
6. Fujioka, A, Takashima, N, Shigeyoshi, Y. Circadian rhythm generation in a glioma cell line. Biochem Biophys Res Commun. 2006; 346 (1): 16974.CrossRefGoogle Scholar
7. Perou, CM, Serlie, T, Eisen, MB, van de Rijn, M, Jeffrey, SS, Rees, CA, et al. Molecular portraits of human breast tumours. Nature. 2000; 406 (6797): 74752.CrossRefGoogle ScholarPubMed
8. Lerebours, F, Lidereau, R. Molecular alterations in sporadic breast cancer. Crit Rev Oncol Hematol. 2002; 44 (2): 12141.CrossRefGoogle ScholarPubMed
9. Widschwendter, M, Jones, PA. DNA methylation and breast carcinogenesis. Oncogene. 2002; 21 (35): 546282.CrossRefGoogle ScholarPubMed
10. Balsalobre, A. Clock genes in mammalian peripheral tissues. Cell Tissue Res. 2002; 309 (1): 1939.CrossRefGoogle ScholarPubMed
11. Reppert, SM, Weaver, DR. Molecular analysis of mammalian circadian rhythms. Annu Rev Physiol. 2001; 63: 64776.CrossRefGoogle ScholarPubMed
12. Metz, RP, Qu, X, Laffin, B, Earnest, D, Perter, WW. Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary gland. Dev Dyn. 2006; 235 (1): 26371.CrossRefGoogle ScholarPubMed
13. Chen, ST, Choo, KB, Hou, MF, Yeh, KT, Kuo, SJ, Chang, JG. Deregulated expression of the Per1, Per2, Per3 genes in breast cancers. Carcinogenesis. 2005; 26 (7): 12416.CrossRefGoogle ScholarPubMed
14. Filipski, E, King, VM, Li, X, Granda, TG, Mormont, MC, Liu, X, et al. Host circadian clock as a control point in tumor progression. J Natl Cancer Inst. 2002; 94 (9): 6907.CrossRefGoogle ScholarPubMed
15. Yeh, KT, Yang, MY, Liu, TC, Chen, JC, Chan, WL, Lin, SF, et al. Abnormal expression of Period 1 (Per1) in endometrial carcinoma. J Pathol. 2005; 206 (1): 11120.CrossRefGoogle ScholarPubMed
16. Hua, H, Wang, Y, Wan, C, Liu, Y, Zhu, B, Wang, X, et al. Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther. 2007; 14 (9): 81518.CrossRefGoogle ScholarPubMed
17. Tcrpe, HJ, Storkel, S, Zimmer, U, Anquez, V, Fischer, C, Pantel, K, et al. Expression of CD44 isoforms in renal cell tumors. Am J Pathol. 1996; 148 (2): 45363.Google Scholar
18. Bjarnason, GA, Jordan, R. Circadian variation of cell proliferation and cell cycle protein expression in man: clinical implications. Prog Cell Cycle Res. 2000; 4: 193206.CrossRefGoogle ScholarPubMed
19. Matsuo, T, Yamaguchi, S, Mitsui, S, Emi, A, Shimoda, F, Okamura, H. Control mechanism of the circadian clock for timing of cell division in vivo. Science. 2003; 302 (5643): 2559.CrossRefGoogle ScholarPubMed
20. Smaaland, R, Lote, K, Sothern, RB, Laerum, OD. DNA synthesis and ploidy in non-Hodgkin’s lymphomas demonstrate intrapatient variation depending on circadian stage of cell sampling. Cancer Res. 1993; 53: 312938.Google ScholarPubMed
21. Panda, S, Antoch, MP, Miller, BH, Su, AI, Schock, AB, Straume, M, et al. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 2002; 109 (3): 30720.CrossRefGoogle ScholarPubMed
22. Storch, KF, Lipan, O, Leykin, I, Viswanathan, N, Davis, FC, Wong, WH, et al. Extensive and divergent circadian gene expression in liver and heart. Nature. 2002; 417 (6884): 7883.CrossRefGoogle ScholarPubMed
23. Duffield, GE, Best, JD, Meurers, BH, Bittner, A, Loros, JJ, Dunlap, JC. Circadian programs of transcriptional activation, signaling, and protein turnover revealed by microarray analysis of mammalian cells. Curr Biol. 2002; 12 (7): 5517.CrossRefGoogle ScholarPubMed
24. Kornmann, B, Preitner, N, Rifat, D, Fleuury-Olela, F, Schibler, U. Analysis of circadian liver gene expression by ADDER, a highly sensitive method for the display of differentially expressed mRNAs. Nucl Acids Res. 2001; 29 (11): E51.CrossRefGoogle ScholarPubMed
25. Le Minh, N, Damiola, F, Tronche, F, Schutz, G, Schibler, U. Glucocorticoid hormones inhibit food-induced phaseshifting of peripheral circadian oscillators. EMBO J. 2001; 20 (24): 712836.CrossRefGoogle ScholarPubMed
26. Hrushesky, WJM, Bjarnason, GA. Circadian cancer therapy. J Clin Oncol. 1993; 11 (7): 140317.CrossRefGoogle ScholarPubMed
27. Levi, F. Circadian chronotherapy for human cancers. Lancet Oncol. 2001; 2 (5): 30715.CrossRefGoogle ScholarPubMed
28. Focan, C. Circadian rhythms and cancer chronotherapy. Pharmacol Ther. 1995; 67 (1): 152.CrossRefGoogle Scholar
29. Mormont, MC, Levi, F. Cancer chronotherapy: principle, applications and perspectives. Cancer. 2003; 97 (1): 15569.CrossRefGoogle Scholar
30. Fu, L, Pelicano, H, Liu, J, Huang, P, Lee, C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002; 111 (1): 4150.CrossRefGoogle ScholarPubMed
31. Lee, CC. Tumor suppression by the mammalian Period genes. Cancer Causes Control. 2006; 17 (4): 52530.CrossRefGoogle ScholarPubMed