Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres.
Cell Rep
; 19(12): 2544-2556, 2017 06 20.
Article
em En
| MEDLINE
| ID: mdl-28636942
ABSTRACT
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative. Here, we show that a subset of high-risk neuroblastomas (with â¼50% 5-year mortality) lacked significant TLM activity. Cancer cells derived from these highly aggressive tumors initially had long telomeres and proliferated for >200 population doublings with ever-shorter telomeres. This indicates that prevention of telomere shortening is not always required for oncogenesis, which has implications for inhibiting TLMs for cancer therapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proliferação de Células
/
Encurtamento do Telômero
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article