Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour

التفاصيل البيبلوغرافية
العنوان: Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour
المؤلفون: Zhang, Hanzhao, Konjusha, Dardan, Rafati, Nima, Tararuk, Tatsiana, Hallböök, Finn, 1962
المصدر: Cellular Oncology. 47(1):209-227
مصطلحات موضوعية: Animal model, Chicken, E2F, Intraocular cancer, MYCN, RB1 proficient, Retinoblastoma
الوصف: PurposeRetinoblastoma, a childhood cancer, is most frequently caused by bi-allelic inactivation of RB1 gene. However, other oncogenic mutations such as MYCN amplification can induce retinoblastoma with proficient RB1. Previously, we established RB1-proficient MYCN-overexpressing retinoblastoma models both in human organoids and chicken. Here, we investigate the regulatory events in MYCN-induced retinoblastoma carcinogenesis based on the model in chicken.MethodsMYCN transformed retinal cells in culture were obtained from in vivo MYCN electroporated chicken embryo retina. The expression profiles were analysed by RNA sequencing. Chemical treatments, qRT-PCR, flow cytometry, immunohisto- and immunocytochemistry and western blot were applied to study the properties and function of these cells.ResultsThe expression profile of MYCN-transformed retinal cells in culture showed cone photoreceptor progenitor signature and robustly increased levels of E2Fs. This expression profile was consistently observed in long-term culture. Chemical treatments confirmed RB1 proficiency in these cells. The cells were insensitive to p53 activation but inhibition of E2f efficiently induced cell cycle arrest followed by apoptosis.ConclusionIn conclusion, with proficient RB1, MYCN-induced high level of E2F expression dysregulates the cell cycle and contributes to retinoblastoma carcinogenesis. The increased level of E2f renders the cells to adopt a similar mechanistic phenotype to a RB1-deficient tumour.
وصف الملف: electronic
URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-522867
https://doi.org/10.1007/s13402-023-00863-0
https://uu.diva-portal.org/smash/get/diva2:1836859/FULLTEXT01.pdf
قاعدة البيانات: SwePub
الوصف
DOI:10.1007/s13402-023-00863-0