Although the administration of retinoids represents an important part of treatment for children suffering from high-risk neuroblastomas, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment. Our study focused on the comparative analysis of the expression of five genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of clinical response to retinoid differentiation therapy. Expression of these five candidate biomarkers was evaluated at both the mRNA and protein level in the same subset of 8 neuroblastoma cell lines after treatment with natural or synthetic retinoids. We found that the cell lines that were HMGA2-positive and/or HOXC9-negative have a reduced sensitivity to retinoids. Furthermore, the experiments revealed that the retinoid-sensitive cell lines showed a uniform pattern of change after treatment with both natural and sensitive retinoids: increased DDX39A and decreased PBX1 protein levels. Our results showed that in NBL cells, these putative protein biomarkers are associated with sensitivity or resistance to retinoids, and their endogenous or induced expression can distinguish between these two phenotypes.
- MeSH
- antitumorózní látky farmakologie MeSH
- bexaroten farmakologie MeSH
- biomarkery farmakologické metabolismus MeSH
- chemorezistence účinky léků genetika MeSH
- DEAD-box RNA-helikasy genetika metabolismus MeSH
- dítě MeSH
- fenretinid farmakologie MeSH
- fixace tkání MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- isotretinoin farmakologie MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové buněčné linie MeSH
- nádory nervového systému genetika metabolismus patologie chirurgie MeSH
- neuroblastom genetika metabolismus patologie chirurgie MeSH
- novorozenec MeSH
- pre-B-buněčný leukemický transkripční faktor 1 genetika metabolismus MeSH
- předškolní dítě MeSH
- proliferace buněk účinky léků MeSH
- protein HMGA1A genetika metabolismus MeSH
- protein HMGA2 genetika metabolismus MeSH
- tretinoin analogy a deriváty farmakologie MeSH
- zalévání tkání do parafínu MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH