Telomerase Activity in Urethane-Induced Mouse Lung Tumorigenesis

ABSTRACT

BACKGROUND: Telomerase activity in precancerous conditions of lung adenocarcinomas has not been well studied. This study is designed to investigate the role of telomerase in premalignant lesions of urethane-induced mouse lung adenocarcinoma. METHODS: We harvested A/J mouse lung tissues at 3, 6, 9, 12, 28, 41, and 48 weeks after intraperitoneal urethane treatment, and classified each lesion in terms of histologic findings. We examined telomerase activity using a modified version of the telomeric repeat amplification protocol assay using both gel-based and enzyme linked immunosorbent assay methods. An immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was performed. RESULTS: In urethane-induced mouse lung tissues, it was sequentially developed from hyperplasia, adenoma, and eventually to adenocarcinoma. Telomerase activity began to show a positive level in tissues with no histologically visible nodule after urethane administration. It revealed a statistically significant increase in hyperplasia compared to the "control" lung tissue (p<0.05), which was proportionally elevated relative to adenoma and adenocarcinoma. There was a direct correlation between telomerase activity and the PCNA labeling index (p<0.05). CONCLUSIONS: The elevation of telomerase activity in normal-appearing lung lesions is thought to be a possible marker of early detection of pulmonary adenocarcinoma.