| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Hamon Center for Therapeutic Oncology Research [K. Y., I. I. W., A. F. G.], Departments of Cell Biology and Neuroscience [M. A. P., J. W. S.] and Pathology [T. R., S. M., A. F. G.], and Veterans Affairs Medical Center [T. R.], The University of Texas Southwestern Medical Center, Dallas, Texas 75235-8593; Department of Pathology [L. A. L.] and Division of Cardiothoracic Surgery [L. K.], The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-4283; British Columbia Cancer Agency, Vancouver, British Columbia, BC-V5Z-3J5 Canada [S. L.]; and Early Detection Research Network, National Cancer Institute, Bethesda, Maryland 20892 [S. S.]
To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (30 of 36; 83%). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in 23% of peripheral lung samples (in epithelium of small bronchi and bronchioles or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up-regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion.
1 This work was supported in part by Contract N01-CN-45580-01, Early Detection Research Network, National Cancer Institute, and Specialized Program of Research Excellence Grant 1-P50-CA70907-01 from the National Cancer Institute.
2 Present address: Geron Corp., 200 Constitution Drive, Menlo Park, CA 94025.
3 To whom requests for reprints should be addressed, at Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8593. Phone: (214) 648-4921; Fax: (214) 648-4924; E-mail: gazdar@simmons.swmed.edu.
Received 3/ 4/97. Accepted 4/29/97.
This article has been cited by other articles:
|
|
 |
|
  Y. Cao, L. I. Huschtscha, A. S. Nouwens, H. A. Pickett, A. A. Neumann, A. C-M. Chang, C. D. Toouli, T. M. Bryan, and R. R. Reddel Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels Cancer Res., May 1, 2008; 68(9): 3115 - 3123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nishio, K. Nakanishi, Y. Ozeki, S.-X. Jiang, T. Kameya, A. Hebisawa, M. Mukai, W. D. Travis, T. J. Franks, and T. Kawai Telomere Length, Telomerase Activity, and Expressions of Human Telomerase mRNA Component (hTERC) and Human Telomerase Reverse Transcriptase (hTERT) mRNA in Pulmonary Neuroendocrine Tumors Jpn. J. Clin. Oncol., January 1, 2007; 37(1): 16 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hajj, T. Baranek, R. Le Naour, P. Lesimple, E. Puchelle, and C. Coraux Basal Cells of the Human Adult Airway Surface Epithelium Retain Transit-Amplifying Cell Properties Stem Cells, January 1, 2007; 25(1): 139 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kedde, C. le Sage, A. Duursma, E. Zlotorynski, B. van Leeuwen, W. Nijkamp, R. Beijersbergen, and R. Agami Telomerase-independent Regulation of ATR by Human Telomerase RNA J. Biol. Chem., December 29, 2006; 281(52): 40503 - 40514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dutu, S. Michiels, P. Fouret, F. Penault-Llorca, P. Validire, S. Benhamou, E. Taranchon, L. Morat, D. Grunenwald, T. Le Chevalier, et al. Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers Ann. Onc., December 1, 2005; 16(12): 1906 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Miyazu, T. Miyazawa, K. Hiyama, N. Kurimoto, Y. Iwamoto, H. Matsuura, K. Kanoh, N. Kohno, M. Nishiyama, and E. Hiyama Telomerase Expression in Noncancerous Bronchial Epithelia Is a Possible Marker of Early Development of Lung Cancer Cancer Res., November 1, 2005; 65(21): 9623 - 9627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lantuejoul, J. C. Soria, L. Morat, P. Lorimier, D. Moro-Sibilot, L. Sabatier, C. Brambilla, and E. Brambilla Telomere Shortening and Telomerase Reverse Transcriptase Expression in Preinvasive Bronchial Lesions Clin. Cancer Res., March 1, 2005; 11(5): 2074 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Tsao, E. S. Kim, and W. K. Hong Chemoprevention of Cancer CA Cancer J Clin, May 1, 2004; 54(3): 150 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K M Fong, Y Sekido, A F Gazdar, and J D Minna Lung cancer * 9: Molecular biology of lung cancer: clinical implications Thorax, October 1, 2003; 58(10): 892 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. Massion and D. P. Carbone From Clinical and Pathologic to Molecular Staging of Lung Cancer Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1587 - 1588. [Full Text] [PDF]
|
|
|
|
|
|
K. Nakanishi, T. Kawai, F. Kumaki, S. Hiroi, M. Mukai, E. Ikeda, C. E. Koering, and E. Gilson Expression of mRNAs for Telomeric Repeat Binding Factor (TRF)-1 and TRF2 in Atypical Adenomatous Hyperplasia and Adenocarcinoma of the Lung Clin. Cancer Res., March 1, 2003; 9(3): 1105 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Soria, X. Xu, D. D. Liu, J. J. Lee, J. Kurie, R. C. Morice, F. Khuri, L. Mao, W. K. Hong, and R. Lotan Retinoic Acid Receptor {beta} and Telomerase Catalytic Subunit Expression in Bronchial Epithelium of Heavy Smokers J Natl Cancer Inst, January 15, 2003; 95(2): 165 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Brambilla, F. Fievet, M. Jeanmart, F. de Fraipont, S. Lantuejoul, V. Frappat, G. Ferretti, P.Y. Brichon, and D. Moro-Sibilot Early detection of lung cancer: role of biomarkers Eur. Respir. J., January 1, 2003; 21(39_suppl): 36S - 44s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C O'Flatharta, M Leader, E Kay, S R Flint, M Toner, W Robertson, and M J E M F Mabruk Telomerase activity detected in oral lichen planus by RNA in situ hybridisation: not a marker for malignant transformation J. Clin. Pathol., August 1, 2002; 55(8): 602 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Pastorino Molecular Targeting: the New Challenge in Lung Cancer Prevention J Natl Cancer Inst, August 15, 2001; 93(16): 1190 - 1191. [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Soria, C. Moon, L. Wang, W. N. Hittelman, S. J. Jang, S.-Y. Sun, J. J. Lee, D. Liu, J. M. Kurie, R. C. Morice, et al. Effects of N-(4-Hydroxyphenyl)retinamide on hTERT Expression in the Bronchial Epithelium of Cigarette Smokers J Natl Cancer Inst, August 15, 2001; 93(16): 1257 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ohno, Y. Horio, Y. Sekido, Y. Hasegawa, M. Takahashi, J.-i. Nishizawa, H. Saito, F. Ishikawa, and K. Shimokata Telomerase activation and p53 mutations in urethane-induced A/J mouse lung tumor development Carcinogenesis, May 1, 2001; 22(5): 751 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K M Kerr Pulmonary preinvasive neoplasia J. Clin. Pathol., April 1, 2001; 54(4): 257 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sueoka, N. Sueoka, Y. Goto, S. Matsuyama, H. Nishimura, M. Sato, S. Fujimura, H. Chiba, and H. Fujiki Heterogeneous Nuclear Ribonucleoprotein B1 as Early Cancer Biomarker for Occult Cancer of Human Lungs and Bronchial Dysplasia Cancer Res., March 1, 2001; 61(5): 1896 - 1902. [Abstract] [Full Text]
|
|
|
|
|
|
F. R. Hirsch, W. A. Franklin, A. F. Gazdar, and P. A. Bunn Jr. Early Detection of Lung Cancer: Clinical Perspectives of Recent Advances in Biology and Radiology Clin. Cancer Res., January 1, 2001; 7(1): 5 - 22. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Ohmura, M. Aoe, A. Andou, and N. Shimizu Telomerase Activity and Bcl-2 Expression in Non-Small Cell Lung Cancer Clin. Cancer Res., August 1, 2000; 6(8): 2980 - 2987. [Abstract] [Full Text]
|
|
|
|
|
|
W. N. ROM, J. G. HAY, T. C. LEE, Y. JIANG, and K.-M. TCHOU-WONG Molecular and Genetic Aspects of Lung Cancer Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1355 - 1367. [Full Text]
|
|
|
|
 |
|
 P. Rudolph, C. Schubert, S. Tamm, K. Heidorn, A. Hauschild, I. Michalska, S. Majewski, G. Krupp, S. Jablonska, and R. Parwaresch Telomerase Activity in Melanocytic Lesions : A Potential Marker of Tumor Biology Am. J. Pathol., April 1, 2000; 156(4): 1425 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Heine, S. E Coupland, S. Kneiff, G. Demel, N. Bornfeld, M. Hummel, and H. Stein Telomerase expression in uveal melanoma Br. J. Ophthalmol., February 1, 2000; 84(2): 217 - 223. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Lau, L. Xue, R. Hu, T. Liaw, R. Wu, and S. Reddy Expression and Regulation of a Molecular Marker, SPR1, in Multistep Bronchial Carcinogenesis Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 92 - 96. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. M. Fong, Y. Sekido, and J. D. Minna MOLECULAR PATHOGENESIS OF LUNG CANCER J. Thorac. Cardiovasc. Surg., December 1, 1999; 118(6): 1136 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yi, V. M. Tesmer, I. Savre-Train, J. W. Shay, and W. E. Wright Both Transcriptional and Posttranscriptional Mechanisms Regulate Human Telomerase Template RNA Levels Mol. Cell. Biol., June 1, 1999; 19(6): 3989 - 3997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Shay Toward Identifying a Cellular Determinant of Telomerase Repression J Natl Cancer Inst, January 6, 1999; 91(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
S. Niho, T. Yokose, K. Suzuki, T. Kodama, Y. Nishiwaki, and K. Mukai Monoclonality of Atypical Adenomatous Hyperplasia of the Lung Am. J. Pathol., January 1, 1999; 154(1): 249 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakano, E. Watney, and J. K. McDougall Telomerase Activity and Expression of Telomerase RNA Component and Telomerase Catalytic Subunit Gene in Cervical Cancer Am. J. Pathol., September 1, 1998; 153(3): 857 - 864. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
