Attivazione del sistema Wnt in linee cellulari di medulloblastoma umano: valutazione della risposta biologica e della risposta alle radiazioni ionizzanti

Ronchi, Alice (2011) Attivazione del sistema Wnt in linee cellulari di medulloblastoma umano: valutazione della risposta biologica e della risposta alle radiazioni ionizzanti, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia e patologia sperimentale: progetto n. 1 "Oncologia", 23 Ciclo. DOI 10.6092/unibo/amsdottorato/3290.
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Abstract

Medulloblastoma (MB) is a paediatric malignant brain tumour, sensitive to ionizing radiations (IR). However radiotherapy has detrimental effects on long-term survivors and the tumour is incurable in a third of patients, due to intrinsic radioresistance. Alterations of the Wnt pathway distinguish a molecular subgroup of MBs and nuclear beta-catenin, indicative of activated Wnt, is associated with good outcome in MB. Therefore there are increasing evidences about Wnt involvement in radio-response: IR induce activation of Wnt signalling with nuclear translocation of beta-catenin in MB cell lines. We studied effects of Wnt pathway activation in a MB cell line with p53 wild-type: UW228-1. Cells were stably transfected with a beta-catenin constitutively active and assessed for growth curves, mortality rate, invasiveness and differentiation. Firstly, activation of Wnt pathway by itself induced a slower cell growth and a higher mortality. After IR treatment, nuclear beta-catenin further inhibited cell growth, increasing mortality. Cell invasiveness was strongly inhibited by Wnt activation. Furthermore, Wnt cell population was characterized by club shaped cells with long cytoplasmic extensions containing neurofilaments, suggesting a neural differentiation of this cell line. These findings suggest that nuclear beta-catenin may leads to a less aggressive phenotype and increases radio-sensitivity in MB, accounting for its favourable prognostic value. In the future, Wnt/beta-catenin signalling will be considered as a molecular therapeutic target to develop new drugs for the treatment of MB.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Ronchi, Alice
Supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Ciclo
23
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
WNT medulloblastoma beta-catenin
URN:NBN
DOI
10.6092/unibo/amsdottorato/3290
Data di discussione
3 Maggio 2011
URI

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