This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakanishi, K. Articles by Gilson, E. Search for Related Content PubMed PubMed Citation Articles by Nakanishi, K. Articles by Gilson, E.

Expression of mRNAs for Telomeric Repeat Binding Factor (TRF)-1 and TRF2 in Atypical Adenomatous Hyperplasia and Adenocarcinoma of the Lung

Division of Environmental Medicine, National Defense Medical College Research Institute, Tokorozawa 359-8513, Japan [K. N.]; Department of Pathology, National Defense Medical College, Tokorozawa 359-8513, Japan [T. K., F. K., S. H.]; Division of Diagnostic Pathology, [M. M.] and Pathology [E. I.], Keio University School of Medicine, Tokyo 160-8582, Japan; and Laboratoire de Biologie Moléculaire et Cellulaire de l’Ecole Normale Supérieure de Lyon, UMR 5665 CNRS/ENSL, 69364 Lyon Cedex 07, France [C. E. K., E. G.]

Purpose and Experimental Design: It has been suggested that atypical adenomatous hyperplasia (AAH) may be a precursor of peripheral adenocarcinoma of the lung. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity is thought to participate in the development of most human cancers. Telomere-specific DNA-binding proteins, such as telomeric repeat binding factor 1 and telomeric repeat binding factor 2, also control telomere length in a complex interplay with telomerase. Here we investigated the expressions of the mRNAs encoded by the TERF1 and TERF2 genes using in situ hybridization in surgically resected specimens [28 AAHs (11 lesions were interpreted as low-grade AAH, and 17 were interpreted as high-grade AAH) and 40 peripherally located bronchioloalveolar carcinoma (BAC).

Results: A clear overexpression of these mRNAs was recognized in low- and high-grade AAH and BAC samples (as compared with normal tissues) using in situ hybridization and these mRNAs were detected in normal AAH and BAC samples using reverse transcription-PCR. The expressions of TERF1 and TERF2 mRNA detected by in situ hybridization were scored positive in 36% and 82% of low-grade AAH, 65% and 83% of high-grade AAH, and 88% and 88% of BAC, respectively. Statistically significant differences in TERF1 mRNA expression could be shown between low-grade AAH and BAC and between high-grade AAH and BAC. There was no statistical difference in the positive expressions of TERF2 mRNA among low-grade AAH, high-grade AAH, and BAC.

Conclusions: These results are consistent with (but are not enough to confirm) the idea that high-grade AAH is closely related to BAC.

This article has been cited by other articles:

				C. M. Raynaud, S. J. Jang, P. Nuciforo, S. Lantuejoul, E. Brambilla, N. Mounier, K. A. Olaussen, F. Andre, L. Morat, L. Sabatier, et al. Telomere shortening is correlated with the DNA damage response and telomeric protein down-regulation in colorectal preneoplastic lesions Ann. Onc., July 17, 2008; (2008) mdn405v1. [Abstract] [Full Text] [PDF]

				D. Poncet, A. Belleville, C. t'Kint de Roodenbeke, A. Roborel de Climens, E. Ben Simon, H. Merle-Beral, E. Callet-Bauchu, G. Salles, L. Sabatier, J. Delic, et al. Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia Blood, February 15, 2008; 111(4): 2388 - 2391. [Abstract] [Full Text] [PDF]

				X. Lin, J. Gu, C. Lu, M. R. Spitz, and X. Wu Expression of telomere-associated genes as prognostic markers for overall survival in patients with non-small cell lung cancer. Clin. Cancer Res., October 1, 2006; 12(19): 5720 - 5725. [Abstract] [Full Text] [PDF]

				B.-K. Oh, Y.-J. Kim, C. Park, and Y. N. Park Up-Regulation of Telomere-Binding Proteins, TRF1, TRF2, and TIN2 Is Related to Telomere Shortening during Human Multistep Hepatocarcinogenesis Am. J. Pathol., January 1, 2005; 166(1): 73 - 80. [Abstract] [Full Text] [PDF]