Die Rolle von ARID1A in Pankreas- und kolorektalem Karzinom

by Jacobe Traub née Rapp
Doctoral thesis
Date of Examination:2023-06-07
Date of issue:2023-05-23
Advisor:Prof. Dr. Steven Johnsen
Referee:Prof. Dr. Steven Johnsen
Referee:Prof. Dr. Matthias Dobbelstein
Persistent Address: http://dx.doi.org/10.53846/goediss-9886

 

 

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Abstract

English

Overall, ARID1A showed a strongly context-dependent function in this study (Sun et al. 2017). In particular, in pancreatic tumors, the tumor suppressive function of ARID1A could be partially confirmed in terms of growth rate. However, regarding potential therapeutic interventions, some questions remain unanswered; here, further studies should follow to clarify the pathomechanism behind the lack of efficacy of EZH2 inhibition and thus, if necessary, find other agents that may provide potential therapeutic options. Regarding the gemcitabine effect on the L3.6pl cell line used here, a very good response to already low doses of the chemotherapeutic agent was shown for the first time. For colorectal carcinomas, dependence on KRAS mutations was shown to be an important factor for the mode of action of ARID1A (Sen et al. 2019). In addition, EMT markers demonstrated an increased metastatic propensity with ARID1A loss. The main task of the study was also to establish models that can represent ARID1A loss and thus be available for further experiments. At the time of the experiments performed, an ARID1A knockout did not represent an established or published system. Within the scope of this work, we were able to establish both a temporary ARID1A knockdown using siRNA and a permanent ARID1A knockout using CRISPR/CAS9. The models generated in this work should be used for further studies to better understand the respective function and associated therapeutic option regarding ARID1A.
Keywords: ARID1A; SWI/SNF; pancreatic tumor; colorectal tumor
 
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