| dc.contributor.advisor | Johnsen, Steven Prof. Dr. | |
| dc.contributor.author | Böcker, Simon Joseph | |
| dc.date.accessioned | 2021-09-02T11:03:43Z | |
| dc.date.available | 2022-10-03T00:50:13Z | |
| dc.date.issued | 2021-09-02 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0008-58FA-C | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8796 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Die Rolle des Chromatinmodulators CHD1 im kastrationsresistenten Prostatakarzinom | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | The role of the chromatin remodeling protein CHD1 in castration resistant prostate cancer | de |
| dc.contributor.referee | Johnsen, Steven Prof. Dr. | |
| dc.date.examination | 2021-10-05 | |
| dc.description.abstracteng | Current therapy of metastasized prostate cancer largely depends on androgen-deprivation therapy (ADT). Despite initial response, tumors inevitably reach castration resistance (CRPC), a stage at which chemotherapy and second-generation anti-androgens like Abiraterone and Enzalutamide represent the main remaining therapeutic options. Acquired resistance to these drugs is an emerging problem, raising a need for new approaches. Loss of Chromodomain Helicase DNA binding protein 1 (CHD1) seems to be more prevalent in CRPC compared to earlier tumor stages. In our work, we identified a correlation between androgen-independent growth and CHD1 depletion in LNCaP prostate cancer cells. Using RNA sequencing, we showed a correlation between CHD1 knockdown and upregulation of Enhancer of Zeste Homolog 2 (EZH2) which could be confirmed at protein level. Treatment with a specific EZH2 inhibitor(1 µM JQ-EZ ) showed a stronger effect on the proliferation of CHD1-depleted cells compared to controls. To further characterize this association, as well as the genome-wide binding profiles, we performed chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) for CHD1 and EZH2 as well as for the histone modifications H3K4me3, H3K27me3 and H3K27ac in normal FBS as well as in charcoal-stripped serum (CSS). We hereby propose a newly discovered synthetic lethality which, in the future, might be exploited for treatment of prostate cancer, e.g. in patients ineligible for chemotherapeutics. | de |
| dc.contributor.coReferee | Trojan, Lutz Prof. Dr. | |
| dc.subject.eng | CHD1 | de |
| dc.subject.eng | prostate cancer | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0008-58FA-C-8 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.description.embargoed | 2022-10-03 | |
| dc.identifier.ppn | 1769347992 | |