Fukushima Mitsuhiro, Shimomura Naotaka, Nakamura Ken-Ichi, Kammori Makoto, Koizumi Kiyoshi, Shimizu Kazuo, Takubo Kaiyo
Department of Clinical Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Oncol Rep. 2004 Dec;12(6):1227-32.
Telomerase activity is present in most malignant tumors and provides a mechanism for unlimited replication of neoplastic cells. This study was undertaken to investigate the expression of the gene encoding human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene in lung carcinoma, by in situ hybridization (ISH). hTERT is associated with telomerase activity, and overexpressed in most lung carcinomas. We assayed hTERT gene expression by ISH to study telomerase activity in lung carcinomas of 27 patients, and compared these results with those of telomerase activity by telomeric repeat amplification protocol (TRAP) assay. TERT gene expression by ISH was detected mainly in the nuclei of lung carcinoma cells. Some specimens showed a significant expression in only infiltrating lymphocytes. hTERT gene expression by ISH was found in 16 of 27 (59%) cases. On the other hand, telomerase activity by TRAP assay was detected in 21 of 27 (78%) cases. In 7 cases, TRAP assay detected telomerase activity, but ISH did not detect hTERT expression. TRAP assay might detect telomerase activity in not only carcinoma cells, but also in infiltrating lymphocytes. Our findings therefore suggest that ISH-based analysis of hTERT gene expression is superior to TRAP assay as a means of determining telomerase status during carcinogenesis.
端粒酶活性存在于大多数恶性肿瘤中，为肿瘤细胞的无限复制提供了一种机制。本研究旨在通过原位杂交（ISH）研究肺癌中编码人端粒酶逆转录酶（hTERT）的基因的表达，hTERT是端粒酶催化亚基基因。hTERT与端粒酶活性相关，且在大多数肺癌中过表达。我们通过ISH检测hTERT基因表达，以研究27例肺癌患者的端粒酶活性，并将这些结果与通过端粒重复序列扩增法（TRAP）检测的端粒酶活性结果进行比较。ISH检测到的TERT基因表达主要在肺癌细胞核中。一些标本仅在浸润淋巴细胞中显示出显著表达。ISH检测到27例中的16例（59%）有hTERT基因表达。另一方面，TRAP检测在27例中的21例（78%）检测到端粒酶活性。在7例中，TRAP检测到端粒酶活性，但ISH未检测到hTERT表达。TRAP检测可能不仅能检测癌细胞中的端粒酶活性，还能检测浸润淋巴细胞中的端粒酶活性。因此，我们的研究结果表明，基于ISH的hTERT基因表达分析作为一种在致癌过程中确定端粒酶状态的方法优于TRAP检测。
