Telomere dysfunction in aging and cancer

Gilley, David; Tanaka, Hiromi; Herbert, Brittney‐Shea

doi:10.1016/j.biocel.2004.09.003

Cited by 79 publications

(62 citation statements)

References 114 publications

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“…The rate of telomere shortening per cell division is not constant and may be a function of oxidative stress and antioxidant defenses (3). Cells with critically truncated telomeres exhibit chromosomal rearrangements and undergo senescence and eventually apoptosis (4). Mouse models indicate an increased incidence of tumor formation with shorter telomeres (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

McGrath

Wong

Michaud

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

301

251

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Truncated telomeres are among the defining characteristics of most carcinomas. Given the role of telomeres in tumorigenesis, we reasoned that constitutionally short telomeres might be associated with an increased risk of bladder cancer. Using quantitative real-time PCR, we measured relative telomere length in bladder cancer cases and healthy controls and evaluated the association between telomere length, cigarette smoking, and bladder cancer risk in a case-control study nested within the Health Professionals Follow-up Study and a case-control study nested within the Nurses' Health Study. Telomeres were significantly shorter in bladder cancer cases (n = 184) than in controls (n = 192). The mean relative telomere length in cases was 0.23 (SD, 0.16) versus 0.27 (SD, 0.15) in controls (P = 0.001). The adjusted odds ratio for bladder cancer was 1.88 (95% confidence interval, 1.05, 3.36) for individuals in the quartile with the shortest telomeres as compared with individuals in the quartile with the longest telomeres (P trend = 0.006). We observed a statistically significant difference in telomere length among men and women (P < 0.001); however, the interaction between gender, telomere length, and bladder cancer risk was not significant. We also observed a significant difference in telomere length across categories of pack-years of smoking (P = 0.01). These findings suggest that truncated telomeres are associated with an increased risk of bladder cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(4):815 -9)

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Section: Introductionmentioning

confidence: 99%

Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

McGrath

Wong

Michaud

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

301

251

View full text Add to dashboard Cite

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“…It ensures the complete replication of chromosome ends, impart protection to ends from nucleolytic degradation, end-toend fusion, and guide the localization of chromosomes within the nucleus (Muniyappa and Kironmai, 1998). Recent studies have implicated key roles for telomeres in diverse cellular processes such as regulation of gene expression, cell division, cell senescence, and cancer (Pays, 1985;Greider, 1992;Allsopp et al, 1995;Vaziri and Benchimol, 1996;Muniyappa and Kironmai, 1998;Gilley et al, 2005). A ribonucleoprotein complex, telomerase, is responsible for extending telomere ends and thus maintains telomere length (Greider and Blackburn, 1985;Morin, 1989).…”

Section: Introductionmentioning

confidence: 99%

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFβ

Tack

Liu

et al. 2005

Oncogene

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Telomerase is induced in certain pathological conditions such as cancer and tissue injury and repair. This induction in fibroblasts from injured lung is repressed by TGFβ via yet unknown mechanisms. In this study, the role of Smad3 in the inhibition of telomerase reverse transcriptase (TERT) gene transcription by TGFβ was investigated. The rat TERT (rTERT) gene promoter was cloned by PCR amplification and fused with a luciferase reporter gene. This construct was used to analyze regulation of promoter acticity in fibroblasts isolated from bleomycin‐injured lung with induced telomerase activity. The results showed that TGFβ inhibited rTERT transcription while stimulating Smad3 expression. Interestingly, TGFβ also inhibited the expression of c‐myc. Co‐transfection with a Smad3 expressing plasmid further repressed rTERT transcription and c‐myc expression, while co‐transfection with the corresponding anti‐sense Smad3 construct had the opposite effect. Mutation of an E‐box in the rTERT promoter suppressed its activity, which could be further reduced by TGFβ treatment. In contrast mutation at a Smad binding element enhanced promoter activity whose inhibition by TGFβ treatment was impaired. Thus TGFβ inhibition of rTERT gene expression was directly mediated by Smad3 via the Smad binding element, while c‐myc appears to primarily regulate its constitutive or induced expression.

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“…Cawthon et al [Cawthon et al, 2003] showed that individuals with shorter telomeres had significantly poor survival due to higher mortality rate caused by heart and infectious diseases. Progressive shortening of telomeres leads to senescence, apoptotic cell death, or oncogenic transformation of somatic cells in various tissues [Gilley et al, 2005;von Zglinicki et al, 2002]. Telomere length, which can be affected by various lifestyle factors, may determine overall health, lifespan, and the rate at which an individual is aging [Babizhayev et al, 2010].…”

Section: Telomere Length Decreases With Age and May Predict Lifespanmentioning

confidence: 99%

Telomeres and Lifestyle Choices

Avcı¹

2012

Reviews on Selected Topics of Telomere Biology

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Telomere dysfunction in aging and cancer

Cited by 79 publications

References 114 publications

Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFβ

Telomeres and Lifestyle Choices

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