Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung

Shibuya, Kiyoshi; Fujisawa, Takehiko; Hoshino, Hidehisa; Baba, Masayuki; Saitoh, Yukio; Iwamoto, Toshihiko; Sekine, Yasuo; Suzuki, Makoto; Hiroshima, Kenzo; Ohwada, Hayato

doi:10.1002/1097-0142(20010815)92:4<849::aid-cncr1392>3.0.co;2-4

Cited by 36 publications

(29 citation statements)

References 23 publications

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“…The results of our study are comparable with those of Kim et al (24), who demonstrated hTERT mRNA in 87.5% of cases with moderate and severe dysplasia in the oral cavity. In agreement with these observations, Shibuya et al (31) found a progressive increase of hTERT mRNA with the degree of epithelial abnormalities during bronchal carcinogenesis; hTERT mRNA was present in 35% of dysplastic lesions and 100% of invasive squamous cell carcinomas.…”

Section: Normal Laryngeal Epithelium and Simple And Abnormal Hyperplasiasupporting

confidence: 57%

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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Section: Normal Laryngeal Epithelium and Simple And Abnormal Hyperplasiasupporting

confidence: 57%

Telomerase Reactivation Is an Early Event in Laryngeal Carcinogenesis

et al. 2003

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“…Although the hTERT mRNA expression RQ-RT-PCR detection method that we used represents only an indicator of the expression level of telomerase mRNA, not a direct assay for the presence of active telomerase, some recent studies have shown a close correlation between hTERT expression and telomerase activity, the expression of hTERT subunit being the limiting factor for telomerase activity. 26,31,32 Moreover, the RQ-RT-PCR is the most sensitive, accurate, and adaptable RNA quantitative technique. 30 We showed that elevation of hTERT mRNA expression correlates with severity of histological changes, which is in general concordance with previous studies performed on surgical resection specimens or in a group of patients with a previous malignancy and unknown smoking status.…”

Section: Discussionmentioning

confidence: 99%

“…30 We showed that elevation of hTERT mRNA expression correlates with severity of histological changes, which is in general concordance with previous studies performed on surgical resection specimens or in a group of patients with a previous malignancy and unknown smoking status. 26,33 In addition to these studies, our data encompass quite a large cohort of heavy smokers with a different morphological pattern of preinvasive lesions, invasive carcinoma, and bronchial epithelium exhibiting normal appearance or bronchitic changes. The vast majority of studies showed a direct association between telomerase activity and transformed cells in surgically resected lung carcinomas, 25,34,35 with <0.5% of telomerase-positive normal cells.…”

Section: Discussionmentioning

confidence: 99%

“…25 Studies reporting hTERT mRNA expression were almost exclusively performed on tumor samples in comparison with normal tissue samples in resection specimens. Shibuya et al 26 studied changes in telomerase activity and hTERT expression in bronchoscopically excised preneoplastic lesions in patients with suspicious or diagnosed lung malignancy. In the current study, we determined the hTERT mRNA expression by using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) in a cohort of heavy smokers who had decreased forced-expiration volume in a variety of preneoplastic bronchial lesions, invasive carcinomas, and morphologically normal bronchial epithelia, and we assessed the significance of hTERT mRNA expression compared with molecular changes in chromosomal regions of DNA-repair genes and cell-cycle regulators, p15 and p16.…”

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confidence: 99%

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Loss of heterozygosity and human telomerase reverse transcriptase (hTERT) expression in bronchial mucosa of heavy smokers

Čapková

Kalinová

Krsková

et al. 2007

Cancer

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We performed surface modification of ultra‐high‐molecular‐weight polyethylene (UHMWPE) through chromic acid etching with the aim of improving the performance of UHMWPE's composites with poly(ethylene terephthalate) fibers. In part I of this study, we evaluated the effects of chemical modification on the surface properties of UHMWPE with X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle measurements. The thermal properties, rheology, and sintering behavior of the modified UHMWPE were compared to those of the base material. XPS and FTIR analysis confirmed the presence of carboxyl and hydroxyl groups on the surface of the modified powders. The substitution of polar groups into the backbone of the polymer decreased its contact angles with water and hexadecane and increased its surface energy, as evidenced by contact angle measurements. The modified UHMWPE was more crystalline than the base resin and less prone to thermal degradation. Although the rheological properties were virtually identical, the modified powders sintered more readily, presumably due to their higher surface energy, which suggested enhanced processability by compression molding. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006

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“…Therefore, elevated hTERT mRNA levels represent a surrogate marker of increased telomerase activity in most cancers and their precursor lesions (13,14). Increased telomerase activity and hTERT mRNA levels are found in virtually all NSCLCs and are proportional to increasing severity of preneoplastic bronchial lesions (15)(16)(17). Notably, an increased hTERT mRNA level in biopsies of preneoplastic endobronchial lesions is associated with an increased relative risk of bronchial cancer or carcinoma in situ (18).…”

Section: Introductionmentioning

confidence: 99%