© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 16, 1257-1263,
August 15, 2001
© 2001 Oxford University Press
REPORT |
Effects of N-(4-Hydroxyphenyl)retinamide on hTERT Expression in the Bronchial Epithelium of Cigarette Smokers
Affiliations of authors: J.-C. Soria, C. Moon, L. Wang, S. J. Jang, S.-Y. Sun, J. M. Kurie, J. S. Lee, W. K. Hong, L. Mao (Molecular Biology Laboratory, Department of Thoracic/Head and Neck Medical Oncology), W. N. Hittelman (Department of Experimental Therapeutics), J. J. Lee, D. Liu (Department of Biostatistics), R. C. Morice (Department of Thoracic and Cardiovascular Surgery), The University of Texas M. D. Anderson Cancer Center, Houston.
Correspondence to: Li Mao, M.D., Molecular Biology Laboratory, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Box 432, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: lmao{at}mdanderson.org).
Background: Telomerase activation plays a critical role in tumorigenesis. To determine the role of telomerase in early lung carcinogenesis and as a potential biomarker in chemoprevention trials, we analyzed the expression of the human telomerase reverse transcriptase catalytic subunit (hTERT) in bronchial biopsy specimens from cigarette smokers who were enrolled in a randomized, double-blinded, placebo-controlled chemoprevention trial of N-(4-hydroxyphenyl)retinamide (4-HPR). Methods: We obtained biopsy specimens from six predetermined sites in the bronchial tree from the 57 participants, before treatment and 6 months after treatment with 4-HPR or placebo. We used in situ hybridization to examine hTERT messenger RNA (mRNA) expression in 266 pretreatment (baseline) and post-treatment site-paired biopsy specimens from 27 patients in the 4-HPR-treated group and from 30 patients in the placebo-treated group. All statistical tests were two-sided. Results: At baseline, 62.4% (95% confidence interval [CI] = 53.9% to 71%) of the biopsy specimens obtained from the group treated with 4-HPR and 65.2% (95% CI = 57.4% to 73.1%) of the biopsy specimens obtained from the placebo-treated group expressed hTERT mRNA. After 6 months, 45.6% (95% CI = 36.9% to 54.3%) of the biopsy specimens obtained from the 4-HPR-treated group and 68.1% (95% CI = 60.4% to 75.8%) of the biopsy specimens obtained from the placebo-treated group expressed hTERT mRNA. The reduction in hTERT expression observed between the two treatment groups over time was statistically significant (P = .01) when we used the biopsy site as the unit of analysis, but not when we used the individual as the unit of analysis (P = .37). Conclusions: Telomerase is frequently reactivated in the lungs of cigarette smokers. The modulation of hTERT expression in 4-HPR-treated smokers suggests that a novel molecular mechanism underlies the potential chemopreventive properties of 4-HPR. hTERT expression is a promising potential biomarker for risk assessment and for the evaluation of the efficacy of chemopreventive agents in lung carcinogenesis.
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