Telomerase and neuroblastoma tumor fate
type: Dataset
description: Telomerase is a ribonucleoprotein consisting of an RNA component (hTR) that serves as atemplate for the addition of telomeric sequences at the ends of chromosomes and a proteincomponent catalytic activity of reverse transcriptase (hTERT). The reactivation of telomerase in 90%of cancers compensates the shortening of telomeres, allowing the immortalization and survival oftumor cells. This canonical role of telomerase is now well documented. However recent studiessuggest that telomerase may have other functions beyond its role in maintaining telomere length intumorigenesis and / or tumor progression.In neuroblastoma (NB), increased levels of telomerase activity (TA) is associated withadvanced disease and poor prognosis. Indeed, several studies have shown that aggressiveneuroblastomas have a high level of TA while favourable tumors, have little or no TA. Therefore, lowtelomerase activity appears to be linked with regression or maturation of NB as it can be seen in theparticular group of 4S stage neuroblastoma. These observations suggest that telomerase may play acrucial role in the development of NB.To better understand the involvement of telomerase in the aggressive phenotype of malignantneuroblasts and drug resistance, we characterized the phenotypic and genotypic changes induced byinhibition of telomerase via ectopic expression of a mutant dominant negative catalytically inactive(DN-hTERT) in a metastatic chemoresistant NB cell line IGR-N-9. Our results show that theexpression of this mutant induces a stromal-type cell differentiation a sensitization to apoptosis inresponse to three cytotoxic agents (cisplatin, staurosporine, TRAIL). The chemosensitization is not theresult of telomere shortening but probably f a modulation of the expression of certain genes involved inthe apoptotic response (re-expression of caspase 8 and wild-type p53), suggesting a noncanonicalfunction of telomerase Furthermore, we showed that hTERT actively regulates the expression ofMYCN. Indeed,…
identifier: NNT: 2011PA11T039
issued: 2026-05-15T18:05:58.736805
language: fr
modified: 2026-05-15T18:05:58.736811
contact point: Organization
  fn: CCSD
keyword: apoptose
keyword: apoptosis
keyword: differenciation
keyword: differentiation
keyword: infoeu-reposemanticsdoctoralthesis
keyword: mycn
keyword: n-myc
keyword: neuroblastoma
keyword: neuroblastome
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: telomerase
keyword: theses
keyword: tumorigenese
keyword: tumorigenesis
landing page: https://theses.hal.science/tel-00708221

Telomerase and neuroblastoma tumor fate
type: Distribution
format: HTML
issued: 2026-05-15T18:05:58.741247
modified: 2026-05-15T18:05:58.707939
access URL: https://theses.hal.science/tel-00708221

test_moissonnage_selune
type: Agent