Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-19T06:31:27.936Z Has data issue: false hasContentIssue false
  • English
  • Français

Telomerase inhibition alters telomere maintenance mechanisms in laryngeal squamous carcinoma cells

Published online by Cambridge University Press:  20 April 2010

W Chen ,
S M Chen ,
Y Yu ,
B K Xiao ,
Z W Huang  and
Z Z Tao
W Chen
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
S M Chen
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
Y Yu
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
B K Xiao
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
Z W Huang
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
Z Z Tao*
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China
*
Address for correspondence: Dr Zezhang Tao, Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. Fax: (86)027 88042292 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background and purpose:

Telomere length must be maintained throughout cancer cell progression and proliferation. In most tumours, telomerase activity maintains telomere length. Therefore, telomerase is a target for cancer treatments. However, some cancer cells maintain telomere length through an alternative mechanism termed ‘alternative lengthening of telomeres’. To determine how telomerase inhibition relates to the initiation of the alternative lengthening of telomeres pathway, we investigated telomerase activity and telomere maintenance in Hep-2 cells with and without reduced telomerase activity.

Materials and methods:

We investigated telomerase activity levels in a normal Hep-2 cell line and in residual cells following telomerase inhibition treatment. Additionally, we looked for expression of a marker protein for the alternative lengthening of telomeres mechanism.

Results and conclusions:

In the residual cells, telomerase activity was eliminated. However, these cells had higher levels of the alternative lengthening of telomeres biomarker, suggesting an alternative mechanism for telomere maintenance following telomerase inhibition. These results could have a major impact on the design of new cancer treatments.

Keywords

Larynx NeoplasmsSquamous CarcinomaTelomerase
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 124 , Issue 7 , July 2010 , pp. 778 - 783
Copyright
Copyright © JLO (1984) Limited 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Marciniak, R, Guarente, L. Human genetics. Testing telomerase. Nature 2001;413:370–1, 373CrossRefGoogle ScholarPubMed
2Mennuni, C, Ugel, S, Mori, F, Cipriani, B, Iezzi, M, Pannellini, T et al. Preventive vaccination with telomerase controls tumor growth in genetically engineered and carcinogen-induced mouse models of cancer. Cancer Res 2008;68:9865–74Google Scholar
3Feldser, DM, Greider, CW. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell 2007;11:461–9CrossRefGoogle ScholarPubMed
4Gillis, AJ, Schuller, AP, Skordalakes, E. Structure of the Tribolium castaneum telomerase catalytic subunit TERT. Nature 2008;455:633–7CrossRefGoogle ScholarPubMed
5Zinn, RL, Pruitt, K, Eguchi, S, Baylin, SB, Herman, JG. hTERT is expressed in cancer cell lines despite promoter DNA methylation by preservation of unmethylated DNA and active chromatin around the transcription start site. Cancer Res 2007;67:194–201CrossRefGoogle ScholarPubMed
6Marciniak, RA, Cavazos, D, Montellano, R, Chen, Q, Guarente, L, Johnson, FB. A novel telomere structure in a human alternative lengthening of telomeres cell line. Cancer Res 2005;65:2730–7CrossRefGoogle Scholar
7Nittis, T, Guittat, L, Stewart, SA. Alternative lengthening of telomeres (ALT) and chromatin: is there a connection? Biochimie 2008;90:5–12Google Scholar
8Chen, SM, Tao, ZZ, Hua, QQ, Xiao, BK, Xu, Y, Wang, Y et al. Inhibition of telomerase activity in cancer cells using short hairpin RNA expression vectors. Cancer Invest 2007;25:691–8CrossRefGoogle ScholarPubMed
9Wang, Y, Duan, HG, Chen, SM, Xiao, BK, Cheng, J, Tao, ZZ. Effect of RNA interference targeting human telomerase reverse transcriptase on telomerase and its related protein expression in nasopharyngeal carcinoma cells. J Laryngol Otol 2007;121:476–82Google Scholar
10Venturini, L, Erdas, R, Costa, A, Gronchi, A, Pilotti, S, Zaffaroni, N et al. ALT-associated promyelocytic leukaemia body (APB) detection as a reproducible tool to assess alternative lengthening of telomere stability in liposarcomas. J Pathol 2008;214:410–14Google Scholar
11Ohali, A, Avigad, S, Naumov, I, Goshen, Y, Ash, S, Yaniv, I. Different telomere maintenance mechanisms in alveolar and embryonal rhabdomyosarcoma. Genes Chromosomes Cancer 2008;47:965–70CrossRefGoogle ScholarPubMed
12Bollmann, FM. Targeting ALT: the role of alternative lengthening of telomeres in pathogenesis and prevention of cancer. Cancer Treat Rev 2007;33:704–9Google Scholar
13Bechter, OE, Zou, Y, Walker, W, Wright, WE, Shay, JW. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res 2004;64:3444–51CrossRefGoogle ScholarPubMed
14Kumakura, S, Tsutsui, TW, Yagisawa, J, Barrett, JC, Tsutsui, T. Reversible conversion of immortal human cells from telomerase-positive to telomerase-negative cells. Cancer Res 2005;65:2778–86CrossRefGoogle ScholarPubMed
15Grobelny, JV, Kulp-McEliece, M, Broccoli, D. Effects of reconstitution of telomerase activity on telomere maintenance by the alternative lengthening of telomeres (ALT) pathway. Hum Mol Genet 2001;10:1953–61CrossRefGoogle ScholarPubMed
16Perrem, K, Colgin, LM, Neumann, AA, Yeager, TR, Reddel, RR. Coexistence of alternative lengthening of telomeres and telomerase in hTERT-transfected GM847 cells. Mol Cell Biol 2001;21:3862–75CrossRefGoogle ScholarPubMed
17Vulliamy, T, Marrone, A, Goldman, F, Dearlove, A, Bessler, M, Mason, PJ et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001;413:432–5Google Scholar