肺癌组织端粒酶亚基的表达及与端粒酶活性的关系

Correlation between Expression of Human Telomerase Subunits and Telomerase Activity in Lung Cancer Tissues

目的：探讨肺癌端粒酶各亚基的表达及与端粒酶活性的关系。方法：用ＴＲＡＰ法检测端粒酶活性，用逆转录 ＰＣＲ（ＲＴ－ＰＣＲ）法检测肺癌组织、肺部良性瘤样病变和病灶旁非癌肺组织的 ＲＮＡ成分（ｈｕｍａｎ ｔｅｌｏｍｅｒａｓｅ ＲＮＡｃｏｍｐｏｎｅｎｔ， ｈＴＲ）、端粒酶逆转录酶（ｈｕｍａｎ ｔｅｌｏｍｅｒａｓｅ ｒｅｖｅｒｓｅ ｔｒａｎｓｃｒｉｐｔａｓｅ， ｈＴＥＲＴ）、端粒酶相关蛋白 １（ｈｕｍａｎｔｅｌｏｍｅｒａｓｅ－ａｓｓｏｃｉａｔｅｄ ｐｒｏｔｅｉｎ， ｈＴＥＰ1）各亚基的 ｍＲＮＡ表达，其结果与肺癌的组织类型、分化程度及ＴＮＭ分期进行了比较。结果：肺癌组织、肺部良性瘤样病变、病灶旁非癌肺组织端粒酶活性阳性率为８２％（４８／５９）、４３％（３／７）和２０％（７／３５）（Ｐ＜０．０００１），ｈＴＥＲＴ ｍＲＮＡ表达阳性率分别为９１％（３３／３６）、７７％（７／９）、３５％（８／２２）（Ｐ＜０．０００１）。３组ｈＴＲ、ｈＴＥＰ１ ｍＲＮＡ普遍呈阳性表达，差异无显著性（Ｐ＞０．０５）。肺癌不同细胞类型（鳞癌和腺癌）、ＴＮＭ分期和分化程度之间端粒酶活性、ｈＴＥＲＴ ｍＲＮＡ水平未见显著差异（Ｐ＞０．０５）。肺癌组织、肺部良性瘤样?

Objective: This study was designed to investigate the relationship between the expression of telomerase subunits and telomerase activity in lung cancer tissues. Method: In lung cancer tissues, benign phymatoid lesions, and adjacent non-cancer lung tissues, telomerase activity was determined by telomeric repeat amplification protocol (TRAP) assay, and the expression of human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and human telomerase-associated protein(hTEP1 ) mRNA were detected with reverse transcriptase-PCR (RT-PCR). The results were compared with the histological types, degree of differentiation, and TNM stage of lung cancer. Results: Positive rate of telomerase activity in lung cancer tissues, benign phymatoid lesions, and adjacent non-cancer lung tissues were 82% (48/ 59), 43% (3/7), and 20% (7/35 ), respectively (P < 0. 0001 ). hTERT mRNA was expressed in 91 % (33 /36) of lung cancer and 77% (7/9 ) of benign phymatoid lesion, whereas only 35 % (8/22 ) in adjacent non-cancer lung tissues (P < 0. 0001 ). hTR, hTEP1 mRNA were commonly expressed in three different tissue groups(P > 0. 05). No significant differences were observed for telomerase activity, and hTEHT mRNA between squamous-cell carcinoma and adenocarcinoma as well as among different stage, and differentiation of lung cancer (P > 0. 05). Combining all lung cancer. benign phymatoid lesion, and adjacent non-cancer lung tissues, 54 (84. 37% ) of 64 cases were concordant for telomerase activity and hTERT mRNA expression (P <0. 001 ). While there was no significant correlation between telomerase activity and hTR or hTEP1 mRNA expression. Conclusions: The present data provide strong evidence that the expression of hTERT may be a rate-limiting determinant of the enzymatic activity of human telomerase and the up-regulation of hTERT expression may play a critical role in lung cancer. Telomerase activity detected by TRAP assay and hTERT mRNA expression by RT-PCR could he a potential diagnostic marker for lung cancer, but the diagnostic specialty is not high enough. It is not useful for predicting state and malignancy in lung cancer.