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Evaluating the Impact of NFκB on the Loss of Apoptosis Induction by TP53 in clear cell Renal Cell Carcinoma (ccRCC)
- Clear cell renal cell carcinoma is the most frequent malignant kidney tumor in adults. It is often associated with biallelic VHL mutations. We characterized our cell lines according to their HIF expression pattern. Cell lines RCC4, UOK-220 and CaKi-2 were assigned to subtype H1H2, cell lines 786-O and A-498 were assigned to subtype H2 and cell lines CaKi-1 and Rc-124 were assigned to subtype VHLwt. Previous work of our group had shown, that p53 can be activated in ccRCC following irradiation but is not able to induce apoptosis. An important link to p53 activity with strong antiapoptotic qualities is the NFB pathway, which can be activated e. g. by irradiation. We irradiated the three subtypes previously established as well as two control cell lines, SAOS-2 (p53 negative cell line) and HEK 293 (contains functioning p53) with 2 Gy and 10 Gy and analyzed several proteins of the pathway by using western blots. Several target genes with antiapoptotic qualities were analyzed by using rt-PCR. We found, that out of the cell lines analyzed, both control cell lines (SAOS-2, HEK 293) showed the strongest response (activation of the NFB pathway) following irradiation. Among the three ccRCC subtypes the VHLwt cell lines showed the strongest response. H2 cell lines showed almost no response at all. A connection between the missing ability of p53 to induce apoptosis and an induction of transcription factors by the NFB pathway could not be determined. We also could not determine biological differences between the subtypes. We analyzed, whether any NFB proteins were present in the nucleus following irradiation and found, that only p50 homodimers were present in the nucleus. This might point towards p50 homodimers, which have been described to have different characteristics than heterodimers. More research is needed to analyze this important finding.
Author: | Miriam Ophelia Gröber |
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URN: | urn:nbn:de:gbv:9-opus-109757 |
Title Additional (German): | Evaluation des Einflusses von NFκB auf den Verlust der Apoptoseinduktion durch TP53 im klarzelligen Nierenzellkarzinom (ccRCC) |
Referee: | PD Dr. med. Nils Kröger, PD Dr. med. Jennifer Kranz |
Advisor: | PD Dr. med. Nils Kröger |
Document Type: | Doctoral Thesis |
Language: | English |
Year of Completion: | 2024 |
Date of first Publication: | 2024/04/16 |
Granting Institution: | Universität Greifswald, Universitätsmedizin |
Date of final exam: | 2024/04/02 |
Release Date: | 2024/04/16 |
Tag: | NFκB |
GND Keyword: | Hypernephrom, Protein p53 |
Page Number: | 54 |
Faculties: | Universitätsmedizin / Klinik und Poliklinik für Urologie |
DDC class: | 500 Naturwissenschaften und Mathematik / 500 Naturwissenschaften |