The Role of Telomeres in Etoposide Induced Tumour Cell Death

Henry Wellcome Biogerontology Laboratory, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 10/2004; 3(9):1169-76. DOI: 10.4161/cc.3.9.1079
Source: PubMed


Etoposide, a topoisomerase II poison is used in the treatment of a number of solid tumors. Contradictory data exist on the role of the telomere/telomerase complex in etoposide induced apoptosis. Therefore we examined the effects of etoposide treatment in the neuroblastoma cell line SHSY5Y, with very short telomeres and the acute lymphoblastic T cell line 1301, which displays extremely long telomeres. Both short-term and continuous exposure to the drug were examined. Etoposide induced widespread DNA damage followed by DNA damage foci formation and ultimately growth arrest and apoptosis in a concentration-dependent manner. However, length of telomeres and of single stranded telomeric G rich overhangs did not change significantly under the treatments in any cell line. There was no significant induction of single-strand breaks in the G-rich strand of telomeres. Telomerase activity was transiently upregulated under low concentrations of etoposide, while high concentrations resulted in decreased telomerase activity only after onset of apoptosis. Telomerase overexpression protected against etoposide induced apoptosis in fibroblasts. The data suggest that telomeres are not major signal transducers towards growth arrest or apoptosis after etoposide treatment. However, upregulation of telomerase might be part of an attempted adaptative response, which protects cells by a mechanism that might be independent of telomere length maintenance.

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Available from: Gabriele Saretzki
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    • "For example our studies demonstrated a strong correlation between results for TRF and the qPCR method for aTL (r2 = 0.75, p < 0.0001) (Figure 2). The TRF measurement for the 1301 B-cell derived lymphoblastoid cell line, commonly used in Flow-FISH analysis of telomere length was reported to be 80 kb [33]. Using the absolute Real-Time PCR method, we measure the average telomere length for 1301 at 70 kb. "
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