Deregulated expression of the clock genes in gliomas.

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. Using reverse transcription polymerase chain reaction and immunohistochemistry techniques, we examined the expression of the most important clock genes, clock, in 67 gliomas.Our results revealed that asynchronized expression of the clock gene was found in cancerous tissues in comparison with paired non-cancerous tissues. The expression levels of clock mRNA in grade III or IV glioma was significantly different from the surrounding non-tumor tissues (P < 0.01). The difference in the expression of clock in low-grade (grades 1 and II) gliomas and the surrounding non-glioma tissues was insignificant (P > 0.05). The intensity of immunoactivity for Clock in highgrade gliomas was significantly higher than that of low-grade gliomas (r = -0.403, P 5 0.012 , < 0.05), non-tumor tissues around high-grade gliomas (r = -0.376, P = 0.027 < 0.05), while there was no difference in the intensity of immunoactivity for Clock between low-grade gliomas and the surrounding non-tumor tissues (P > 0.05). The expression of PCNA (Proliferating Cell Nuclear Antigen) protein in highgrade gliomas was significantly higher than that of low-grade gliomas (P < 0.05). In this study, we found that the expression of clock in glioma cells and in the surrounding non-tumor cells. The expression of clock in highgrade gliomas was significantly higher than that of the low-grade gliomas and non-glioma. Therefore, we suggest that disturbances in clock expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells and promoting carcinogenesis.