Department of Neurosurgery in the Affiliated Hospital of Ningxia Medical University, Yinchuan, China.
Can J Neurol Sci. 2010 May;37(3):365-70. doi: 10.1017/s031716710001026x.
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 two important clock genes, Per1 and Per2, in 33 gliomas.
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 high-grade gliomas was significantly lower than that in low-grade gliomas(r=-0.433, P=0.012).
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.
越来越多的证据表明，生物钟的失调在恶性肿瘤的发展中起着重要作用，包括神经胶质瘤。然而，控制神经胶质瘤细胞中昼夜节律的基因的分子机制尚未被探索。
我们使用逆转录聚合酶链反应和免疫组织化学技术，检测了 33 例神经胶质瘤中两个重要的时钟基因 Per1 和 Per2 的表达。
在本研究中，33 例神经胶质瘤中，有 28 例 Per1 阳性，有 23 例 Per2 阳性。神经胶质瘤细胞中 Per1 和 Per2 的表达水平与周围非神经胶质瘤细胞明显不同（P<0.01）。高等级（III 级和 IV 级）和低等级（I 级和 II 级）神经胶质瘤中 Per1 和 Per2 的表达率差异无统计学意义（P>0.05）。而高等级神经胶质瘤和低等级神经胶质瘤之间 Per2 免疫活性强度无差异（r=-0.330，P=0.061），高等级神经胶质瘤中 Per1 的表达水平明显低于低等级神经胶质瘤（r=-0.433，P=0.012）。
在这项研究中，我们发现神经胶质瘤细胞中 Per1 和 Per2 的表达明显低于周围的非神经胶质瘤细胞。因此，我们认为 Per1 和 Per2 表达的紊乱可能导致正常昼夜节律控制的破坏，从而有利于神经胶质瘤细胞的存活。昼夜节律基因在神经胶质瘤和非神经胶质瘤细胞中的差异表达可能为神经胶质瘤的化疗提供分子基础。
