Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kral, S.
Investigating the immune regulatory function of Nr4a1 in Myc-driven lymphomagenesis.
[ Diplomarbeit/Master Thesis (UNI) ] Graz University of Technology; 2020. pp.62.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Deutsch Alexander
- Feichtinger Julia
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- Abstract:
- Background: In several studies a tumour suppressive function of Nr4a1 has been demonstrated. The research group of Dr. Alexander Deutsch showed that Nr4a1 works as a tumour suppressor in Myc-driven lymphomagenesis. EµMyc mice with Nr4a1 loss had a faster development of lymphoma and a lower survival rate, compared to EµMyc wildtype mice. Furthermore, they showed that immunogenic genes were differentially expressed in EµMyc Nr4a1-/- tumour, indicating that Nr4a1 regulates immunological pathways in lymphoma. In transplantation experiments the group of Dr. Alexander Deutsch demonstrated that the engraftment of lymphoma in immune-competent C57BI/6 mice, transplanted with EµMyc Nr4a1-/- lymphoma cells, was faster than in C57BI/6 mice, which were transplanted with EµMyc Nr4a1+/+ lymphoma cells, whereas no differences was detected in immune-deficient mice. These data indicate that Nr4a1 significantly impacts on the immune evasion in aggressive lymphoma. Aim: The aim of this project was to characterise mouse cell lines derived from lymphoma of EµMyc Nr4a1-/- and EµMyc Nr4a1+/+ mice by a flow cytometry analysis of cell surface markers. As well as expression analysis of interleukins and immune checkpoints. In the second part of this work expressions levels of different genes implicated in migration, immunologic functions, signalling, apoptosis, autophagy, cell cycle, chromatin remodelling and transcription in lymphoma derived from EµMyc Nr4a1-/- and EµMyc Nr4a1+/+ mice were analysed. Results: Flow cytometry analysis revealed that five cell lines derive from an immature B cell, two from a more mature type expressing IgM. Concerning the expression of checkpoints 13 of 17 were upregulated in cell lines with Nr4a1 loss. Furthermore, two interleukin receptors and one interleukin were found to be upregulated in EµMyc Nr4a1-/- cell lines.V Additionally, in the gene expression analysis of the tumours derived from EµMyc Nr4a1-/- and EµMyc Nr4a1+/+ mice, 4 genes were found to be differentially expressed in tumours with Nr4a1 loss- two genes involved in stimulating immunogenic functions, one gene involved in cell cycle and one gene, which plays a role in regulation of transcription. Conclusion: In conclusion, this work helped to point out the self-generated mouse cell lines, as a potential model for in vitro analysis of lymphoma. Additionally, an effect of Nr4a1 on checkpoints and interleukins could be shown. Furthermore, Nr4a1 might also play a role in regulation of two stimulating immunogenic gene, one gene involved in cell cycle and probably also regulates one gene involved in transcriptional regulation.