Department of Neurosurgery, The First People's Hospital of Jingmen, Jingmen, China.
Technol Cancer Res Treat. 2013 Feb;12(1):91-7. doi: 10.7785/tcrt.2012.500250.
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.
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生物钟的基因的分子机制尚未得到探索。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 67 例神经胶质瘤中最重要的时钟基因 clock 的表达情况。我们的结果表明，与配对的非癌组织相比，癌组织中发现 clock 基因表达不同步。III 级或 IV 级神经胶质瘤中 clock mRNA 的表达水平与周围非肿瘤组织有显著差异（P<0.01）。低级别（1 级和 2 级）神经胶质瘤和周围非神经胶质瘤组织中 clock 表达的差异无统计学意义（P>0.05）。高级别神经胶质瘤中 Clock 的免疫活性强度明显高于低级别神经胶质瘤（r=-0.403，P<0.012，P<0.05），高于高级别神经胶质瘤周围非肿瘤组织（r=-0.376，P=0.027，P<0.05），而低级别神经胶质瘤和周围非肿瘤组织中 Clock 的免疫活性强度无差异（P>0.05）。高级别神经胶质瘤中 PCNA（增殖细胞核抗原）蛋白的表达明显高于低级别神经胶质瘤（P<0.05）。在这项研究中，我们发现 clock 在神经胶质瘤细胞和周围非肿瘤细胞中的表达。高级别神经胶质瘤中 clock 的表达明显高于低级别神经胶质瘤和非神经胶质瘤。因此，我们认为时钟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和促进癌变。
