This Article Full Text Full Text (PDF) Supplementary Data 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 Yokoi, S. Articles by Inazawa, J. Search for Related Content PubMed PubMed Citation Articles by Yokoi, S. Articles by Inazawa, J.

TERC Identified as a Probable Target within the 3q26 Amplicon That Is Detected Frequently in Non-Small Cell Lung Cancers

Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan [S. Y., K. Y., I. I., J. I.]; Department of Thoracic Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan [S. Y., T. I., T. F.]; and CREST, Japan Science and Technology Corporation, Kawaguchi-city, Saitama 332-0012 Japan [K. Y., I. I., J. I.]

ABSTRACT

Purpose: Cell lines derived from non-small cell lung cancers (NSCLCs) revealed frequent high-level gains of chromosomal DNA at 3q23-q29 when examined by comparative genomic hybridization (CGH). Within this amplicon, a minimal common region of amplification in lung tumors had been mapped to 3q26 by earlier studies. The aim of the present work was to identify specific targets of the 3q26 amplification in NSCLCs.

Experimental Design: We examined genomic alterations in 19 NSCLC cell lines (10 derived from squamous cell carcinomas and 9 from adenocarcinomas) by using CGH and fluorescence in situ hybridization. We determined amplification and expression levels of four candidates (EVI1, TERC, SNO, and PIK3CA) in those cell lines and also in 25 primary NSCLC tumors. Because the TERC gene encodes the RNA component of human telomerase, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay.

Results: Copy numbers of EVI1 and TERC increased more than those of SNO and PIK3CA in our panel of NSCLC cell lines. Significant correlation between amplification and expression levels was observed only for TERC (P = 0.006), however, among these four candidate genes. Expression of TERC was also up-regulated in 24 (96%) of 25 primary NSCLC tumors compared with their nontumorous counterparts (P = 0.0001), and elevated expression of TERC was associated with high levels of telomerase activity (P = 0.048).

Conclusions: TERC is a likely target of the 3q26 amplification, and, therefore, may be a useful biomarker for diagnosis and an attractive, novel target for molecular therapy of NSCLC.

This article has been cited by other articles:

				M. N. Chau, L. H. El Touny, S. Jagadeesh, and P. P. Banerjee Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3 Carcinogenesis, November 1, 2007; 28(11): 2282 - 2290. [Abstract] [Full Text] [PDF]

				M. Nanjundan, Y. Nakayama, K. W. Cheng, J. Lahad, J. Liu, K. Lu, W.-L. Kuo, K. Smith-McCune, D. Fishman, J. W. Gray, et al. Amplification of MDS1/EVI1 and EVI1, Located in the 3q26.2 Amplicon, Is Associated with Favorable Patient Prognosis in Ovarian Cancer Cancer Res., April 1, 2007; 67(7): 3074 - 3084. [Abstract] [Full Text] [PDF]

				G. Pelosi, B. Del Curto, M. Trubia, A. G. Nicholson, M. Manzotti, G. Veronesi, L. Spaggiari, P. Maisonneuve, F. Pasini, A. Terzi, et al. 3q26 Amplification and Polysomy of Chromosome 3 in Squamous Cell Lesions of the Lung: A Fluorescence In situ Hybridization Study Clin. Cancer Res., April 1, 2007; 13(7): 1995 - 2004. [Abstract] [Full Text] [PDF]

				J. S. Sunde, H. Donninger, K. Wu, M. E. Johnson, R. G. Pestell, G. S. Rose, S. C. Mok, J. Brady, T. Bonome, and M. J. Birrer Expression Profiling Identifies Altered Expression of Genes That Contribute to the Inhibition of Transforming Growth Factor-{beta} Signaling in Ovarian Cancer. Cancer Res., September 1, 2006; 66(17): 8404 - 8412. [Abstract] [Full Text] [PDF]

				R. J.C. Slebos, Y. Yi, K. Ely, J. Carter, A. Evjen, X. Zhang, Y. Shyr, B. M. Murphy, A. J. Cmelak, B. B. Burkey, et al. Gene Expression Differences Associated with Human Papillomavirus Status in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., February 1, 2006; 12(3): 701 - 709. [Abstract] [Full Text] [PDF]

				R. P. Regala, C. Weems, L. Jamieson, A. Khoor, E. S. Edell, C. M. Lohse, and A. P. Fields Atypical Protein Kinase C{iota} Is an Oncogene in Human Non-Small Cell Lung Cancer Cancer Res., October 1, 2005; 65(19): 8905 - 8911. [Abstract] [Full Text] [PDF]

				H. Izumi, J. Inoue, S. Yokoi, H. Hosoda, T. Shibata, M. Sunamori, S. Hirohashi, J. Inazawa, and I. Imoto Frequent silencing of DBC1 is by genetic or epigenetic mechanisms in non-small cell lung cancers Hum. Mol. Genet., April 15, 2005; 14(8): 997 - 1007. [Abstract] [Full Text] [PDF]

				S. Buonamici, D. Li, F. M. Mikhail, A. Sassano, L. C. Platanias, O. Colamonici, J. Anastasi, and G. Nucifora EVI1 Abrogates Interferon-{alpha} Response by Selectively Blocking PML Induction J. Biol. Chem., January 7, 2005; 280(1): 428 - 436. [Abstract] [Full Text] [PDF]