Original article: general thoracic
Expression of human telomerase subunit genes in primary lung cancer and its clinical significance

https://doi.org/10.1016/S0003-4975(00)01454-5Get rights and content

Abstract

Background. Three major components of human telomerase, RNA component (hTERC), telomerase-associated protein (TEP1), and catalytic subunit (hTERT) have been cloned recently. The aim of this study was to examine the expression of these genes and to search for clinical usefulness.

Methods. Expression of these genes was evaluated by reverse transcription-polymerase chain reaction in 92 human lung cancers and in 32 non-neoplastic lung tissues. In 15 patients, both telomerase activity by telomeric repeat amplification protocol assay and expression were evaluated.

Results. hTERT expression was best associated with telomerase activity with a concordance of 77%. In 92 lung cancer tissues, hTERC, TEP1, and hTERT were expressed in 100%, 93%, and 89%, respectively. Whereas most adjacent non-neoplastic lung tissues expressed hTERC and TEP1 (94% and 100%, respectively), hTERT was detected in only 1 of 32 normal lungs. However, there was no relationship between hTERT expression and clinicopathologic features.

Conclusions. hTERT expression can be a surrogate for telomerase activity that may serve as a novel biomarker of lung cancer with high specificity and sensitivity.

Section snippets

Patients

A total of 92 tumor specimens from patients with primary lung cancer who underwent pulmonary resection at the Department of Thoracic Surgery, Aichi Cancer Center Hospital from November 1990 to September 1998 were examined. All tissue samples were frozen in liquid nitrogen as soon as possible following surgical removal and stored at −70°C until use. The patients were 66 men and 26 women ranging in age from 41 to 80 years old (median 63). The lesions were 55 adenocarcinomas, 27 squamous cell

Relationship between detection of telomerase activity and expression of hTERT, hTEP1, or hTERC

Results for telomerase activity and expression of hTERC, TEP1, and hTERT in 15 specimens from which both RNA and protein extracts from paired non-neoplastic and tumor tissues were available are summarized in Figure 1. Telomerase activity was detected in 80% (12 of 15) of tumor tissues, whereas a significantly smaller number of non-neoplatstic lung tissues (27% [4 of 15]) had telomerase activity (p = 0.0046, Fisher’s exact test). A much clearer difference was observed for hTERT expression,

Comment

Previous reports suggested that hTERT is a key component of telomerase whose expression is strictly associated with telomerase activity in various systems 9, 10, 12. Expression of hTERT has been observed at high levels in telomerase-positive cancer cell lines but not in non-neoplastic tissues, whereas neither TEP1 nor hTERC expression correlates with telomerase activity 9, 10, 12. However, in recent studies of surgical specimens, although expression of hTERT demonstrated the closest association

Acknowledgements

We thank Mitsuko Suzuki for secretarial assistance. This work was supported in part by the Aichi Cancer Research Foundation, the Charitable Trust Soyu Medical Foundation, the Bristol-Meyers Squibb Biomedical Research Grant Program, a Grant-in-Aid (09671403) from the Ministry of Education Science and Culture of Japan, and the Mitsui Life Social Welfare Foundation.

References (23)

  • T.M. Nakamura et al.

    Telomerase catalytic subunit homologs from fission yeast and human

    Science

    (1997)
  • Cited by (48)

    • Template-ready PCR method for detection of human telomerase reverse transcriptase mRNA in sputum

      2019, Analytical Biochemistry
      Citation Excerpt :

      The catalytic activity of telomerase resides in the TERT component, and the regulation of TERT mRNA expression is the critical step for telomerase activation [1–3]. Most somatic cells do not show detectable telomerase activity due to lack of human TERT (hTERT) expression, while the enzyme is expressed in various epithelial tumors including lung cancers [4–16]. Reverse transcription (RT)- Polymerase Chain Reaction (PCR) methods, including the conventional electrophoresis-based and real-time quantitative versions, have been developed to measure levels of hTERT mRNA in tumor tissues for the diagnosis and prognostic prediction of lung cancer [4–7,9–14].

    • Telomerase as a potential marker for inflammation and cancer detection in bronchial washing: A prospective study

      2013, Clinical Biochemistry
      Citation Excerpt :

      Telomerase is a ribonucleotide reverse transcriptase enzyme that elongates the ends of the chromosomes to prevent cell senescence. This enzyme is highly activated in more than 85% of cancers [24] including lung cancer [16,25–32], and in lower intensity in activated lymphocytes, germ and stem cells [33]. Lots of efforts have been deployed in the last two decades in order to study the value of telomerase activity in various types of lung cancer [17,20,21,23–25] most of them are retrospective and targeted studies.

    • Prevalence of telomerase activity in human cancer

      2011, Journal of the Formosan Medical Association
    • Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility

      2009, Lung Cancer
      Citation Excerpt :

      Two independent comparative genomic hybridization studies found increased copy numbers at chromosome 5p15.33 to be associated with non-small cell carcinomas [30] and adenocarcinomas [31]. Other research suggests the clinical importance of TERT expression as a potential biomarker of lung cancer [32,33]. Our study found carriers of the A allele at TERT rs2075786 to be associated with a decreased risk of lung cancer.

    • Telomerase activity in sputum and telomerase and its components in biopsies of advanced lung cancer

      2007, European Journal of Cancer
      Citation Excerpt :

      The RNA component of human telomerase (h-TERC) provides the template for telomere repeat synthesis. Our data confirm that hTERC expression is present in the majority of tumour lung tissues; however, the telomerase activity correlated only with hTERT but not with hTERC, which is in agreement with previous studies.27–29 This indicates that hTERT is the principal regulator of telomerase activity in lung cancer.

    View all citing articles on Scopus
    View full text