Differential responses of human melanoma cells to c-Rel downregulation

Differential responses of human melanoma cells to c-Rel downregulation

Marie Kristin Priebe

Doctoral thesis

Date of Examination: 2020-03-03

Date of issue: 2020-01-29

Advisor: Seitz, Cornelia Sabine Prof. Dr.

Referee: Dobbelstein, Matthias Prof. Dr.

Referee: Oppermann, Martin Prof. Dr.

Persistent Address: http://hdl.handle.net/21.11130/00-1735-0000-0005-12FE-9

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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