摘要
背景与目的:端粒酶逆转录酶(hTERT)和端粒酶相关蛋白1(hTP1)是人端粒酶的重要组成部分。已知胶质瘤细胞有端粒酶异常再活化,而hTERT和hTP1基因表达是否也相应增加,尚不清楚。本研究是为了探讨胶质瘤细胞hTERT和hTP1基因表达、增殖活性及凋亡程度变化的相互关系及其在胶质瘤发生、发展中的作用。方法:采用mRNA原位杂交、免疫组织化学染色及原位细胞凋亡检测(TUNEL)等方法观察了70例不同级别的人胶质瘤组织标本。结果:本组70例胶质瘤hTERTmRNA和蛋白的阳性表达率分别为88.6%和82.9%,WHOI￣II级组、III级组及IV级组间比较二者的阳性表达率均无显著性差异(P>0.05),hTP1mRNA和蛋白及增殖细胞核抗原(PCNA)蛋白的阳性表达率均为100%。以上五种阳性肿瘤细胞的密度彼此间均呈显著性正相关(r=0.589￣0.882,P<0.0005),并均随肿瘤级别升高而相应增加,不同级别组间比较差异均有显著性(P<0.05￣0.01)。凋亡肿瘤细胞的检出率也为100%,但凋亡肿瘤细胞密度随肿瘤级别升高而相应减少,不同级别组间比较差异均有显著性(P<0.01),且与前五种阳性肿瘤细胞密度间均呈显著性负相关(r=-0.551￣-0.775,P<0.0005)。结论:以上指标对评价胶质瘤的生物学行为均有重要参考价值,胶质瘤细胞hTERT和hTP1基因异常表达是其端粒酶再活化的先决条件,后者通过抑制肿瘤细胞衰老凋亡和促进其增殖在胶质瘤的发生、发展过程中均起重要作用。
BACKGROUND＆OBJECTIVES： Human telomerase reverse transcriptase （hTERT） and telomerase-associated protein 1 （hTP1） are the important components of human telomerase. It has been shown that there is abnormal telomerase reactivation in human glioma cells. However, it is still unclear whether expressions of hTERT and hTP1 genes are also relevantly up-regulated with the reactivation. This study was undertaken to investigate the relationship among variations of expressions of hTERT and hTP1 genes. proliferation.and apoptosis of the glioma ceils as weld as effect of these variations on the development and progression of the gliomas. METHODS： The expressions of hTERT mRNA and protein, hTP1 mRNA and protein, and proliferating cell nuclear antigen （PCNA） as well as apoptosis in seventy human glioma specimens with different malignant grades were studied using in situ hybridization, immunohistochemisry and in situ cell death detection （TUNEL method）. RESULTS： The expressions of hTERT mRNA and protein were observed in 62 （88.6%） and 58 （82.9%） of 70 gliomas respectively. Their expression incidences did not appear to be significant difference among different malignant grade gliomas （P〉0.05）. All of these gliomas expressed hTP1 mRNA, hTP1 protein and PCNA （100%）. The quantities of the above five kinds of positive cells were correlated positively with one another （r=0.589-0.882, P〈0.0005）, and all of them were significantly fewer in WHO grade Ⅰ-Ⅱgliomas than in grade Ⅲ gliomas and the most in grade Ⅳ gliomas （P〈 0.05-0.01）. The apoptotic tumor cells were detected in all the specimens （100%）. However, their quantity was more in WHO grade Ⅰ-Ⅱ gliomas than in grade Ⅲ gliomas and the fewest in grade Ⅳ gliomas （P〈0.01）, and was correlated negatively with the former five kinds of positive cells respectively （r=-0.551-0.775, P〈0.0005）. CONCLUSION： These results suggest that all of the above parameters have the important referential value in the evaluation of biological behavior of gliomas. In glioma ceils, abnormal expressions of hTERT and hTP1 genes are precondition of the telomerase reactivation, the latter plays possibly the important roles in the development and malignant progression of gliomas by inhibiting apoptosis of the tumor cells and promoting their proliferation.
出处
《中国神经肿瘤杂志》
2005年第2期82-87,共6页
Chinese Journal of Neuro-Oncology
基金
国家自然科学基金资助项目(项目批准号:39870335)
关键词
胶质瘤
端粒酶逆转录酶
端粒酶相关蛋白
1
细胞增殖
细胞凋亡
Glioma
Human telomerase reverse transcriptase
Human telomerase-associated protein 1
Cell proliferation
Apoptosis
