Abstract
Up-regulation of telomerase has been reported in many cancers. Our aim was to characterize telomerase activity in various states of the oesophagus to facilitate better understanding of carcinogenesis of oesophageal squamous cell carcinoma. During endoscopic examinations, we obtained 45 Lugol-stained normal epithelia, 31 Lugol-unstained epithelia (14 oesophagitis, 7 mild dysplasia, 5 severe dysplasia and 5 intramucosal cancer) and 9 advanced cancer. Telomerase activity was semi-quantified by a telomeric repeat amplification protocol using enzyme-linked immunosorbent assay, and expression of human telomerase reverse transcriptase mRNA was examined by in situ hybridization. In the Lugol-stained normal epithelia, telomerase activity increased in proportion to the increase of severity of the accompanying lesions, with a rank order of advanced cancer, intramucosal cancer, mild dysplasia and oesophagitis. In the Lugol-unstained lesions and advanced cancer, telomerase activity was highest in advanced cancer. Up-regulation of telomerase in normal squamous epithelium may be a marker of progression of oesophageal squamous cell carcinoma. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Bachor C, Bachor OA and Boukamp P (1999) Telomerase is active in normal gastrointestinal mucosa and not up-regulated in precancerous lesions. J Cancer Res Clin Oncol 125: 453–460
Belair CD, Yeager TR, Lopez PM and Reznikoff CA (1997) Telomerase activity: a biomarker of cell proliferation, not malignant transformation. Proc Natl Acad Sci USA 94: 13677–13682
Chadeneau C, Hay K, Hirte HW, Gallinger S and Bacchetti S (1995) Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res 55: 2533–2536
Cheng AJ, Tang R, Wang JY, See LC and Wang TC (1998) Possible role of telomerase activation in the cancer predisposition of patients with hereditary nonpolyposis colorectal cancers. J Natl Cancer Inst 90: 316–321
Cheng AJ, Tang R, Wang JY, Chang JT and Wang TC (1999) Polymerase Chain Reaction-based Enzyme Immunoassay for quantitation of telomerase activity: application to colorectal cancers. Jpn J Cancer Res 90: 280–285
Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159
Dawsey SM, Fleischer DE, Wang GQ, Zhou B, Kidwell JA, Lu N, Lewin KJ, Roth MJ, Tio TL and Taylor PR (1998) Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China. Cancer 83: 220–231
Esteve A, Lehman T, Jiang W, Weinstein IB, Harris CC, Ruol A, Peracchia A, Montesano R and Hollstein M (1993) Correlation of p53 mutations with epidermal growth factor receptor overexpression and absence of mdm2 amplification in human esophageal carcinomas. Mol Carcinog 8: 306–311
Fujimoto K and Takahashi M (1997) Telomerase activity in human leukemic cell lines is inhibited by antisense pentadecadeoxynucleotides targeted against c-myc mRNA. Biochem Biophys Res Commun 241: 775–781
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW and Weinberg RA (1999) Creation of human tumour cells with defined genetic elements. Nature 400: 464–468
Harle-Bachor C and Boukamp P (1996) Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci U S A 93: 6476–6481
Hiyama E, Hiyama K, Tatsumoto N, Kodama T, Shay JW and Yokoyama T (1996) Telomerase activity in human intestine. Int J Oncol 9: 453–458
Hiyama K, Hiyama E, Ishioka S, Yamakido M, Inai K, Gazdar AF, Piatyszek MA and Shay JW (1997) Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst 87: 895–902
Holt SE, Wright WE and Shay JW (1996) Regulation of telomerase activity in immortal cell lines. Mol Cell Biol 16: 2932–2939
Hytiroglou P, Kotoula V, Thung SN, Tsokos M, Fiel MI and Papadimitriou CS (1998) Telomerase activity in precancerous hepatic nodules. Cancer 82: 1831–1838
Ikeguchi M, Unate H, Maeta M and Kaibara N (1999) Detection of telomerase activity in esophageal squamous cell carcinoma and normal esophageal epithelium. Langenbecks Arch Surg 384: 550–555
Japanese Society for Esophageal Disease (1992) Guidelines for the clinical and pathologic studies on carcinoma of the esophagus, 8th ed. Kanehara
Kiaris H and Schally AV (1999) Decrease in telomerase activity in U-87MG human glioblastomas after treatment with an antagonist of growth hormone-releasing hormone. Proc Natl Acad Sci U S A 96: 226–231
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266: 2011–2015
Klapper W, Singh KK, Heidorn K, Parwaresch R and Krupp G (1998) Regulation of telomerase activity in quiescent immortalized human cells. Biochim Biophys Acta 1442: 120–126
Koyanagi K, Ozawa S, Ando N, Takeuchi H, Ueda M and Kitajima M (1999) Clinical significance of telomerase activity in the non-cancerous epithelial region of oesophageal squamous cell carcinoma. Br J Surg 86: 674–679
Koyanagi K, Ozawa S, Ando N, Mukai M, Kitagawa Y, Ueda M and Kitajima M (2000) Telomerase activity as an indicator of malignant potential in iodine-nonreactive lesions of the esophagus. Cancer 88: 1524–1529
Krupp G, Kuhne K, Tamm S, Klapper W, Heidorn K, Rott A and Parwaresch R (1997) Molecular basis of artifacts in the detection of telomerase activity and a modified primer for a more robust ‘TRAP' assay. Nucleic Acids Res 25: 919–921
Kuwano H, Ohno S, Matsuda H, Mori M and Sugimachi K (1988) Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus. Cancer 61: 1635–1638
Lu SH, Hsieh LL, Luo FC and Weinstein IB (1988) Amplification of the EGF receptor and c-myc genes in human esophageal cancers. Int J Cancer 42: 502–505
Mori M, Adachi Y, Matsushima T, Matsuda H, Kuwano H and Sugimachi K (1993) Lugol staining pattern and histology of esophageal lesions. Am J Gastroenterol 88: 701–705
Morin GB (1989) The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59: 521–529
Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB and Cech TR (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277: 955–959
Nakamura Y, Tahara E, Tahara H, Yasui W and Ide T (1999) Quantitative reevaluation of telomerase activity in cancerous and noncancerous gastrointestinal tissues. Mol Carcinog 26: 312–320
Nakanishi Y, Ochiai A, Yoshimura K, Kato H, Shimoda T, Yamaguchi H, Tachimori Y, Watanabe H and Hirohashi S (1998) The clinicopathologic significance of small areas unstained by Lugol's iodine in the mucosa surrounding resected esophageal carcinoma. Cancer 82: 1454–1459
Nakano K, Watney E and McDougall JK (1998) Telomerase activity and expression of telomerase RNA component and telomerase catalytic subunit gene in cervical cancer. Am J Pathol 153: 857–864
Nakayama J, Tahara H, Tahara E, Saito M, Ito K, Nakamura H, Nakanishi T, Tahara E, Ide T and Ishikawa F (1998) Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nat Genet 18: 65–68
Parkin DM, Pisani P and Ferlay J (1999) Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 80: 827–841
Rohde V, Sattler HP, Bund T, Bonkhoff H, Fixemer T, Bachmann C, Lensch R, Unteregger G, Stoeckle M and Wullich B (2000) Expression of the human telomerase reverse transcriptase is not related to telomerase activity in normal and malignant renal tissue. Clin Cancer Res 6: 4803–4809
Schlemper RJ, Dawsey SM, Itabashi M, Iwashita A, Kato Y, Koike M, Lewin KJ, Riddell RH, Shimoda T, Sipponen P, Stolte M and Watanabe H (2000) Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists. Cancer 88: 996–1006
Schrier PI and Peltenburg LT (1993) Relationship between myc oncogene activation and MHC class I expression. Adv Cancer Res 60: 181–246
Shimada Y, Imamura M, Wagata T, Yamaguchi N and Tobe T (1992) Characterization of 21 newly established esophageal cancer cell lines. Cancer 69: 277–284
Sugimachi K, Ohno S, Matsuda H, Mori M, Matsuoka H and Kuwano H (1989) Clinicopathologic study of early stage esophageal carcinoma. Surgery 105: 706–710
Tahara H, Yasui W, Tahara E, Fujimoto J, Ito K, Tamai K, Nakayama J, Ishikawa F, Tahara E and Ide T (1999) Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. Oncogene 18: 1561–1567
Takakura M, Kyo S, Kanaya T, Tanaka M and Inoue M (1998) Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res 58: 1558–1561
Takubo K, Nakamura K, Izumiyama N, Mafune K, Tanaka Y, Miyashita M, Sasajima K, Kato M and Oshimura M (1997) Telomerase activity in esophageal carcinoma. J Surg Oncol 66: 88–92
Taylor RS, Ramirez RD, Ogoshi M, Chaffins M, Piatyszek MA and Shay JW (1996) Detection of telomerase activity in malignant and nonmalignant skin conditions. J Invest Dermatol 106: 759–765
Wang J, Xie LY, Allan S, Beach D and Hannon GJ (1998) Myc activates telomerase. Genes Dev 12: 1769–1774
Wright WE, Shay JW and Piatyszek MA (1995) Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity. Nucleic Acids Res 23: 3794–3795
Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J and Dalla-Favera R (1999) Direct activation of TERT transcription by c-MYC. Nat Genet 21: 220–224
Yashima K, Piatyszek MA, Saboorian HM, Virmani AK, Brown D, Shay JW and Gazdar AF (1997) Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes. J Clin Pathol 50: 110–117
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Maki Inai and Masato Kano equally contributed to this work
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Inai, M., Kano, M., Shimada, Y. et al. Telomerase activity of the Lugol-stained and -unstained squamous epithelia in the process of oesophageal carcinogenesis. Br J Cancer 85, 1006–1013 (2001). https://doi.org/10.1054/bjoc.2001.2032
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DOI: https://doi.org/10.1054/bjoc.2001.2032