Loss of telomerase activity may be a potential favorable prognostic marker in lung carcinomas

Wu, Tzu Chin; Lin, Pei; Hsu, Chiao Po; Huang, Yung-Fu; Chen, Chih Yi; Chung, Wen Chuan; Lee, Huei; Ko, Jiunn‐Liang

doi:10.1016/s0169-5002(03)00195-8

Cited by 41 publications

(35 citation statements)

References 16 publications

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“…Such an association has been reported in mISH (Kumaki et al, 2001;Wang et al, 2002;Fujita et al, 2003;Lantuejoul et al, 2004) and immunohistochemistry studies (Kumaki et al, 2001;Toomey et al, 2001;Lantuejoul et al, 2004). In contrast, the prognostic value of hTERT mRNA expression assayed by RT -qPCR has been inconsistent Hara et al, 2001;Marchetti et al, 2002;Wu et al, 2003;Hsu et al, 2004). Some studies have associated overexpression with poor prognosis Hara et al, 2001;Marchetti et al, 2002;Hsu et al, 2004), while others have failed to do so (Wu et al, 2003).…”

Section: Discussionmentioning

confidence: 85%

“…In contrast, the prognostic value of hTERT mRNA expression assayed by RT -qPCR has been inconsistent Hara et al, 2001;Marchetti et al, 2002;Wu et al, 2003;Hsu et al, 2004). Some studies have associated overexpression with poor prognosis Hara et al, 2001;Marchetti et al, 2002;Hsu et al, 2004), while others have failed to do so (Wu et al, 2003). One possible explanation is that hTERT mRNA has six known splice variants, but only the full-length transcript is functional.…”

Section: Discussionmentioning

confidence: 99%

“…Telomerase activity and/or hTERT expression are increased in cancers and are prognostic factors in various cancer types (Harada et al, 1999;Bieche et al, 2000;Lee et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Krams et al, 2003;Ohali et al, 2003;Tchirkov et al, 2003;Lantuejoul et al, 2004). However, the clinical impact of hTERT expression or activity in non-small-cell lung cancer (NSCLC) remains controversial (Albanell et al, 1997;Taga et al, 1999;Hirashima et al, 2000;Komiya et al, 2000;Toomey et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Wu et al, 2003;Hsu et al, 2004;Lantuejoul et al, 2004). The clinical significance of increased hTERT gene copy number has not been investigated.…”

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confidence: 99%

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Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

et al. 2006

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Telomerase reactivation is a hallmark of human carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. This study evaluates the prognostic value of hTERT gene amplification and mRNA overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens. The hTERT gene copy number was assessed by quantitative polymerase chain reaction (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA level was determined by reverse transcription (RT) -qPCR in 130 tumours. In total, 57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification, which was significantly more common (Po0.001) in adenocarcinoma (30 out of 40) than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell than in adenocarcinoma (87 vs 68%, P ¼ 0.03). Overexpression was significantly associated with amplification (P ¼ 0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio ¼ 2.16, P ¼ 0.03). These data indicate that gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

et al. 2006

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“…In patients with surgically-treated early-stage lung cancer a correlation has been found between a poor prognosis and detection in tumour tissue of either elevated hTERT expression [by RT-PCR (19)(20)(21)(22), immunohistochemistry (23) or ISH (24,25)] or telomerase activity (26)(27)(28)(29). However, data on this topic are not consistent since other studies failed to reveal a correlation between hTERT expression and (diseasefree) survival (28,30,31).…”

Section: Introductionmentioning

confidence: 99%

“…However, data on this topic are not consistent since other studies failed to reveal a correlation between hTERT expression and (diseasefree) survival (28,30,31). The latest study published on the subject even found elevated hTERT mRNA level to be predictive of a better prognosis (32).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

et al. 2010

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Vorinostat, SAHA, represses telomerase activity via epigenetic regulation of telomerase reverse transcriptase in non-small cell lung cancer cells

Hsiao

et al. 2011

J. Cell. Biochem.

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Vorinostat (suberoylanilide hydroxamic acid), a class of histone deacetylase inhibitors, represents an emerging class of anticancer agents currently progressing in clinical trials. It causes cell growth inhibition, differentiation, and apoptosis of many tumor types in vitro and in vivo. Recently, it was reported that hTERT is one of the targets for cancer therapy in cancer cells. Telomerase repeat amplification protocol assay was used to analyze the expression of hTERT after vorinostat treatment in the A549 lung cancer cells. Vorinostat inhibited telomerase activity by reducing the expression of human telomerase reverse transcriptase (hTERT) in A549 human lung cancer cells. The epigenetic regulation mechanism is responsible for the repression of hTERT by vorinostat, analyzed through the methylation-specific PCR and bisulfite sequencing of the hTERT promoter. Vorinostat induced the demethylation of site-specific CpGs on the promoter region of hTERT, which was caused by the down-regulation of DNA methyltransferases. DNA methyltransferases (DNMT1 and DNMT3b) were also decreased in vorinostat-treated A549 cancer cells. Furthermore, chromatin immunoprecipitation analysis of the hTERT promoter revealed that vorinostat decreased the level of inactive chromatin markers dimethyl-H3K9, and the declined binding of DNMT1 and DNMT3b were associated. The novel insights showed that vorinostat down-regulated telomerase via epigenetic alteration in lung cancer to vorinostat-mediated cancer-specific therapies.

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Loss of telomerase activity may be a potential favorable prognostic marker in lung carcinomas

Cited by 41 publications

References 16 publications

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

Vorinostat, SAHA, represses telomerase activity via epigenetic regulation of telomerase reverse transcriptase in non-small cell lung cancer cells

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