Cell cycle-dependent modulation of telomerase activity in tumor cells.

Zhu, Xuemei; Kumar, Rakesh; Mandal, Mahitosh; Sharma, Nitisha; Sharma, Harsh W.; Dhingra, Urvashi; Sokoloski, John A.; Hsiao, R; Narayanan, Ramaswamy

doi:10.1073/pnas.93.12.6091

Cited by 207 publications

(140 citation statements)

References 27 publications

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“…By using a synchronized cell population, it was also shown that telomerase activity was regulated in the cell cycle (Zhu et al, 1996). However, Holt et al (1997) claim that telomerase activity in immortalized cell lines, which is usually detected at high levels, remained constant during the cell cycle when non-cytotoxic cell cycle blockers were used.…”

Section: Discussionmentioning

confidence: 99%

“…One of underlying questions is whether telomerase activity could be regulated during the course of cell growth and di erentiation. Recently, it was shown that telomerase activity was downregulated when cell growth was inhibited by cell cycle inhibitors (Zhu et al, 1996) or the cells became quiescent in vitro (Sharma et al, 1995;Albannell et al, 1996;Bestilny et al, 1996;Holt et al, 1996). These previous studies suggest that telomerase activity is regulated in the process of cell growth and differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Kikuchi

Ahmed

et al. 1998

Oncogene

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Telomerase activity is correlated with the immortality of various cultured cells and cancer cells. The activity, however, is also demonstrated in various normal regenerating cells which normally have a ®nite life span in vivo and in vitro, though its biological implication remains unclear. Using cultured normal human epithelial cells, we show that telomerase activity is associated with epithelial cell subsets which actively proliferate in vitro. Unlike in most cancer cell lines, telomerase activity was evidently up-regulated when the cells entered into S phase in primary human epithelial cells. To characterize the cells which have telomerase activity, the primary human epithelial cell population of uterine cervix was dissociated into several distinctive cellular subsets by means of immunocytochemical cell fractionation. Telomerase activity was found to be closely associated with the subset which expressed predominantly integrin b1 and epidermal growth factor receptor. We further identi®ed the telomerase-negative subpopulation which contained a small subset that strongly coexpresses p75 NGFR low a nity nerve growth factor receptor, integrin b4 and bcl-2 protein. The location of the p75 NGFR -expressing cells contrasts to that of the Ki-67 positive cells in vivo and is distinctive of telomerase positive cycling cells, indicating that these cells remain at the G0 phase. The present study supports the notion that telomerase activity is linked to cell cycle regulation, implying that telomerase is activated upon cell proliferation in regenerating normal human epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Kikuchi

Ahmed

et al. 1998

Oncogene

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“…Thus, in vitro neuronal di erentiation of NPC was associated to a progressive decrease of telomerase activity. Telomerase expression has been shown to be tightly linked to the cell cycle (Zhu et al, 1996). Contrary to neurons, primary astrocytes could proliferate actively in vitro.…”

Section: Telomerase Activity During Cortical and Cerebellar Developmentmentioning

confidence: 99%

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

et al. 2000

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“…Analysis of the distribution of percentage of cells in di erent phases of cell cycle according to cell DNA content was performed on gated nuclei using the software program Holt et al (1996) reported that telomerase is active throughout the cell cycle in dividing, immortal cells but its activity is repressed in G 0 cells. However, Zhu et al (1996) reported that human tumor cells arrested at G 1 /S phase of the cell cycle showed similar levels of telomerase activity to asynchronous cultures, but progression through the S phase was associated with increased activity. To see whether there is any di erential expression of telomerase during di erent phases of cell cycle, cells were assayed at di erent time points after collecting the cells by mitotic shake o method.…”

mentioning

confidence: 99%

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

1997

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Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in ®ve Chinese hamster cell lines following exposure to 5 J/m 2 or 40 J/m 2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCRbased telomeric repeat ampli®cation protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G 2 /M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in di erent phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by¯uorescence in situ hybridization (FISH). This is the ®rst study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.

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Cell cycle-dependent modulation of telomerase activity in tumor cells.

Cited by 207 publications

References 27 publications

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

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