Telomerase Activity Is Upregulated in Laryngeal Squamous Cell Carcinoma

Curran, Aongus J.; Gullane, Patrick; Irish, Jonathan C.; MacMillan, Christina; Freeman, Jeremy L.; Kamel‐Reid, Suzanne

doi:10.1097/00005537-200003000-00011

Cited by 22 publications

(21 citation statements)

References 15 publications

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“…In the carcinogenesis of squamous cell carcinoma in the oral cavity, telomerase reactivation most probably represents an early event and is already detectable in a moderately dysplastic oral squamous epithelium (22). In the larynx, from 68 -100% of laryngeal squamous cell carcinomas show telomerase reactivation (11)(12)(13)(14)(15)(16)(17), although the exact role and timing of telomerase reactivation in laryngeal carcinogenesis are still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that hTERT mRNA may occasionally be detected in a normal laryngeal epithelium, but the frequency and relative quantity of hTERT mRNA is significantly higher in laryngeal squamous cell carcinomas (11). To the best of our knowledge, only six studies to date have been published using a telomeric repeat amplification protocol (TRAP) for the measurement of telomerase activity in the larynx and/or hypopharynx (12)(13)(14)(15)(16)(17). The main drawback of these studies is the lack of uniformly applied terminology for different grades of epithelial abnormalities, as well as imprecise methodology used for detection of telomerase activity.…”

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confidence: 99%

“…Namely, TRAP assay has been identified as having several limitations, because an active telomerase enzyme complex is obligatory for detection of telomerase activity (18). Nevertheless, telomerase activity has been detected in 0 -20% of normal epithelia (12,14,17), 100% of hyperplastic epithelia (17), and 0 -100% of dysplastic epithelia, depending on the degree of epithelial dysplasia (12,16,17), and in 68 -100% of invasive squamous cell carcinomas (12)(13)(14)(15)(16)(17). It can be deduced from these studies that telomerase reactivation represents an important, most probably obligatory event in laryngeal carcinogenesis.…”

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Telomerase Reactivation Is an Early Event in Laryngeal Carcinogenesis

et al. 2003

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The exact role and timing of reactivation of telomerase, a key enzyme implicated in cellular immortalization and transformation in the multistep process of laryngeal carcinogenesis, is still unknown. We attempted to (1) determine that quantitative differences exist in the levels of telomerase catalytic subunit (hTERT) mRNA expression among different grades of laryngeal epithelial abnormalities classified according to the Ljubljana classification; (2) determine that telomerase reactivation is an important, most probably early event in laryngeal carcinogenesis; and (3) analyze whether the relative quantity of hTERT mRNA can be used as a molecular biomarker in the early detection of precancerous lesions. The relative quantity of hTERT mRNA, expressed as an hTERT index, was analyzed in 140 frozen laryngeal tissue specimens representing different morphological stages of laryngeal carcinogenesis by using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. The presence and relative quantity of hTERT mRNA in laryngeal epithelium increases progressively with the degree of epithelial abnormalities. hTERT mRNA was detectable in 1/15 normal laryngeal epithelia (7%, mean hTERT index 0.02), 3/15 simple hyperplasias (20%, mean hTERT index 0.09), 10/27 abnormal hyperplasias (37%, mean hTERT index 0.18), 9/12 atypical hyperplasias (75%, mean hTERT index 0.74), 8/9 intraepithelial carcinomas (89%, mean hTERT index 1.82), and 53/62 invasive laryngeal squamous cell carcinomas (85%, mean hTERT index 2.51). Statistical analysis revealed two groups of laryngeal epithelial changes with significant differences in the levels of hTERT mRNA expression (P < .0033): (1) normal and reactive hyperplastic laryngeal epithelium (simple and abnormal hyperplasia) and (2) atypical hyperplasia (precancerous lesion), intraepithelial and invasive laryngeal squamous cell carcinoma. The results of the present study suggest that telomerase reactivation is an early event in laryngeal carcinogenesis, detectable already at the stage of precancerous laryngeal epithelial changes. Nevertheless, other genetic abnormalities appear to be necessary for progression of these epithelial abnormalities toward invasive laryngeal squamous cell carcinoma.

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Telomerase Reactivation Is an Early Event in Laryngeal Carcinogenesis

et al. 2003

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“…10 Most laryngeal cancer cells persistently express high levels of telomerase activity, whereas a healthy laryngeal epithelium rarely displays it. 11,12 The 2 main components of telomerase are the template human telomerase RNA (TR) and a human telomerase reverse transcriptase (TERT) catalytic subunit. Studies have shown that TERT expression is likely to be the rate-limiting factor in regulating telomerase activity.…”

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confidence: 99%

Application of combination of short hairpin RNA segments for silencing VEGF, TERT, and Bcl-xl expression in laryngeal squamous carcinoma

Wang¹,

Tao²,

Chen³

et al. 2008

Cancer Biology & Therapy

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Results: We demonstrated that a recombinant plasmid containing multiple shRNAs could effectively and simultaneously inhibit VEGF, TERT and Bcl-xl mRNA and protein expression in the HEp-2 cells; the plasmid containing the 3 different shRNAs exhibited a potent antitumor effect on LSCC both in vitro and in vivo, and could much more effectively induced cell apoptosis than each single shRNA. We also demonstrated that the simultaneous blockage of these 3 genes have a better inhibitory effect on human HEp-2 cells than the blockage of each single shRNA. Conclusions Our study demonstrates that the application of vector-based RNAi technology that involves hitting multiple targets will be a promising therapeutic modality in the gene therapy of human laryngeal cancers; furthermore, it provides experimental evidence for the clinical application of this technology in the future.

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“…Eighty-five percent of all cancers are telomerase positive, while for most normal somatic cells, telomerase activity is absent or very low. [4][5][6] Therefore, telomerase is considered an ideal target for cancer therapy, and many strategies have been developed to inhibit telomerase, such as antisense nucleotides, ribozymes, dominant-negative proteins, and small synthetic molecules. 7,8 RNA interference (RNAi) represents an evolutionarily cellular mechanism for controlling expression of genes in almost all eukaryotes, including humans.…”

Section: Introductionmentioning

confidence: 99%