Differential responses of human melanoma cells to c-Rel downregulation

by Marie Kristin Priebe
Doctoral thesis
Date of Examination:2020-03-03
Date of issue:2020-01-29
Advisor:Prof. Dr. Cornelia Sabine Seitz
Referee:Prof. Dr. Matthias Dobbelstein
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-7813

 

 

Files in this item

Name:Dis M Priebe Druckversion ohne Lebenslauf.pdf
Size:1.72Mb
Format:PDF

The following license files are associated with this item:

Abstract

English

The transcription factor NF-κB, which is one of the central regulators regarding cell growth, proliferation, apoptosis, inflammation and invasion, was shown to also play a role in melanoma development and progression. This thesis aimed to further enlighten the role of the NF-κB subunit c-Rel in malignant melanoma. For this purpose, seven melanoma cell lines derived from primary tumor and metastasis were characterized regarding c-Rel expression and growth pattern, revealing varying c-Rel expression levels and growth features. Transient downregulation of c-Rel by siRNA in melanoma cell lines A375 (derived from primary tumor) and LOX (derived from metastasis) led to growth inhibition, suggesting a pro-proliferative function. Altered cell cycle distribution, namely increased portions of cells in G2/M phase and increased numbers of polyploid cells were detected after c-Rel down-regulation in both cell lines. Additionally, c-Rel downregulation leads to an altered mitotic spindle morphology in LOX cells with predominantly monopolar spindle formations. Altogether, these results propose an involvement of c-Rel in cell cycle regulation, thereby suggesting a novel tumor-promoting role in human melanoma cells with putative implications as a new combination target in melanoma therapy.
Keywords: c-Rel; NF-κB; melanoma
 
Statistik