Telomerase activity in small-cell and non-small-cell lung cancers

Keiko Hiyama, Eiso Hiyama, Shinichi Ishioka, Michio Yamakido, Kouki Inai, Adi F. Gazdar, Mieczyslaw A. Piatyszek, Jerry W. Shay

Research output: Contribution to journalArticle

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Abstract

Background: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. Methods: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. Results: Among surgically resected samples, telomerase activity was detected in 109 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-small-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). Conclusion: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)895-901
Number of pages7
JournalJournal of the National Cancer Institute
Volume87
Issue number12
StatePublished - Jun 21 1995

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Lung Cancer
Telomerase
Non-Small Cell Lung Carcinoma
Cells
Tissue
Cell
Tumors
DNA
Cancer
Lung
Small Cell Lung Cancer
Neoplasms
Tumor
Fluids
Biopsy
Polymerase chain reaction
Adjacent
Chromosomes
Lung Neoplasms
Nucleotides

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Telomerase activity in small-cell and non-small-cell lung cancers. / Hiyama, Keiko; Hiyama, Eiso; Ishioka, Shinichi; Yamakido, Michio; Inai, Kouki; Gazdar, Adi F.; Piatyszek, Mieczyslaw A.; Shay, Jerry W.

In: Journal of the National Cancer Institute, Vol. 87, No. 12, 21.06.1995, p. 895-901.

Research output: Contribution to journalArticle

Hiyama, K, Hiyama, E, Ishioka, S, Yamakido, M, Inai, K, Gazdar, AF, Piatyszek, MA & Shay, JW 1995, 'Telomerase activity in small-cell and non-small-cell lung cancers', Journal of the National Cancer Institute, vol. 87, no. 12, pp. 895-901.
Hiyama K, Hiyama E, Ishioka S, Yamakido M, Inai K, Gazdar AF et al. Telomerase activity in small-cell and non-small-cell lung cancers. Journal of the National Cancer Institute. 1995 Jun 21;87(12):895-901.
Hiyama, Keiko ; Hiyama, Eiso ; Ishioka, Shinichi ; Yamakido, Michio ; Inai, Kouki ; Gazdar, Adi F. ; Piatyszek, Mieczyslaw A. ; Shay, Jerry W. / Telomerase activity in small-cell and non-small-cell lung cancers. In: Journal of the National Cancer Institute. 1995 ; Vol. 87, No. 12. pp. 895-901.
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abstract = "Background: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. Methods: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. Results: Among surgically resected samples, telomerase activity was detected in 109 (80.1{\%}) of 136 primary lung cancer tissues and in three (4.4{\%}) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-small-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). Conclusion: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.",
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T1 - Telomerase activity in small-cell and non-small-cell lung cancers

AU - Hiyama, Keiko

AU - Hiyama, Eiso

AU - Ishioka, Shinichi

AU - Yamakido, Michio

AU - Inai, Kouki

AU - Gazdar, Adi F.

AU - Piatyszek, Mieczyslaw A.

AU - Shay, Jerry W.

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N2 - Background: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. Methods: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. Results: Among surgically resected samples, telomerase activity was detected in 109 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-small-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). Conclusion: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.

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