Experimental elongation of telomeres extends the lifespan of immortal x normal cell hybrids.

Wright, Woodring E.; Brasiskyte, D; Piatyszek, Mieczyslaw A.; Shay, Jerry W.

doi:10.1002/j.1460-2075.1996.tb00519.x

Cited by 145 publications

(97 citation statements)

References 58 publications

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“…This activation is dependent on wtp53. Elongation of telomeres after the treatment of immortal cells with G-rich oligonucleotides was also shown in another study (Wright et al, 1996). However, the p53 status of the cell lines examined was not mentioned, nor was whether or not the cells went through a temporary block of proliferation.…”

Section: Discussionmentioning

confidence: 67%

“…Unsynchronized cells were treated daily with oligonucleotides (BioTez Berlin, Germany) in concentrations as indicated for up to 6 consecutive days. The half-life of these oligonucleotides in serum-supplemented medium has been estimated to be 4 ± 6 h (Wright et al, 1996). For some experiments cells were partially synchronized by con¯uence.…”

Section: Chemicals and Treatmentsmentioning

confidence: 99%

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Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

et al. 1999

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It has been repeatedly suspected that telomere shortening might be one possible trigger of the p53-dependent cell cycle arrest, although the mechanism of this arrest remained unclear. Telomeres in human cells under mild oxidative stress accumulate single-strand damage faster than interstitial repetitive sequences. In MRC-5 ®bro-blasts and U87 glioblastoma cells, which both express wild-type p53, oxidative stress-mediated production of single-strand damage in telomeres is concomitant to the accumulation of p53 and p21 and to cell cycle arrest. This response can be modeled by treatment of cells with short single stranded telomeric G-rich DNA fragments. The arrest is transient in U87 cells. Recovery from it is accompanied by up-regulation of telomerase activity and elongation of telomeres. Overexpression of mutated p53 is su cient to reverse the phenotype of inhibition as well as the delayed activation of telomerase. These data suggest that the production of G-rich single stranded fragments during the course of telomere shortening is su cient to trigger a p53 dependent cell cycle arrest.

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Section: Discussionmentioning

confidence: 67%

Section: Chemicals and Treatmentsmentioning

confidence: 99%

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

et al. 1999

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“…Complementation studies of somatic cell hybrids (Pereira-Smith and Smith, 1988) have demonstrated that some immortal6immortal cell fusions may still senesce depending on the cell combinations used and that all mortal6immortal hybrids senesce suggesting that mortality is a dominant trail (Karlsson et al, 1996;Wright et al, 1996). In addition, several studies of cellular senescence induced by microcell chromosome mediated fusion have been reported (Barrett, 1993;Ohmura et al, 1995;Saski et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Telomerase activity during spontaneous immortalization of Li-Fraumeni syndrome skin fibroblasts

Gollahon

Kraus

et al. 1998

Oncogene

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Li-Fraumeni Syndrome (LFS) is characterized by heterozygous germline mutations in the p53 gene. Accompanied by genomic instability and loss or mutation of the remaining wild type p53 allele, a low frequency of spontaneous immortalization in LFS ®broblasts occurs. It is believed that the loss of p53 wild type function contributes to immortalization of these LFS ®broblasts, but it is not clear if this is su cient. Because stabilization of telomere length is also thought to be a necessary step in immortalization, telomerase activity, expression of the telomerase RNA component (hTR) and telomere length were analysed at various passages during the spontaneous immortalization of LFS skin ®broblasts. One LFS strain which immortalized, MDAH087 (087), had no detectable telomerase activity whereas another LFS strain which immortalized, MDAH041 (041), had detectable telomerase activity. In preimmortal cells from both strains, hTR was not detected by in situ hybridization. Immortal 087 cells remained negative for hTR, while immortal 041 cells demonstrated strong hTR in situ hybridization signals. 087 cells had long and heterogenous telomeres whereas telomeres of 041 cells had short, stable telomere lengths. Tumorigenicity studies in nude mice with ras-transformed 087 and 041 cells resulted in both cell lines giving rise to tumors and retaining telomerase status. Overall these results suggest that strain speci®city may be important in telomerase re-activation and that both abrogation of p53 function and a mechanism to maintain telomeres are necessary for immortalization.

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“…[5][6][7][8] Consistently, elongation of telomeres extends the life span of cells in culture. 9 Taken together, immortal cells have to maintain telomere length to continue proliferation, mainly by reactivation of telomerase. 10 Telomerase activity was detected in approximately 85% of various types of cancers including HCC by the telomeric repeat amplification protocol (TRAP), [11][12][13][14][15][16][17] a sensitive assay, whereas most normal somatic cells did not exhibit the activity.…”

mentioning

confidence: 99%

Quantitation of telomerase activity in hepatocellular carcinoma: A possible aid for a prediction of recurrent diseases in the remnant liver

Suda¹,

Isokawa²,

Aoyagi³

et al. 1998

Hepatology

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Because telomerase activity is necessary for cell immortality and probably associated with tumor progression, we have evaluated a possible aid for quantitation of the activity to predict intrahepatic recurrences after surgery in patients with hepatocellular carcinoma (HCC). HCC tissues obtained by surgical resection from 20 patients were studied. Telomerase activity was expressed as peaks with a periodicity through a fluorescence-based telomeric repeat amplification protocol using an autosequencer, and the quantity of activity was calculated from peak areas. A ratio of fluorescence intensity depending on telomerase to that of an internal standard was used as a value of relative telomerase activity (RTA). RTA in serially diluted S100 extracts from HepG2 cells was well correlated with the amount of the extracts. The mean RTA value of 36.4 ؎ 27.8 (mean ؎ SD, 3.21 to 105) in 9 patients suffering from early recurrences after surgery was significantly higher than that (9.84 ؎ 7.65; mean ؎ SD, 3.00 to 29.0) in 11 patients without intrahepatic recurrences during the early period (P ‫؍‬ .004). These results indicate that RTA value can be a useful predictor for intrahepatic recurrences during the early period after surgical resection of HCC. (HEPATOLOGY 1998; 27:402-406.)

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Experimental elongation of telomeres extends the lifespan of immortal x normal cell hybrids.

Cited by 145 publications

References 58 publications

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

Telomerase activity during spontaneous immortalization of Li-Fraumeni syndrome skin fibroblasts

Quantitation of telomerase activity in hepatocellular carcinoma: A possible aid for a prediction of recurrent diseases in the remnant liver

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