The NF-κB signaling pathway in melanoma cells and implications for its therapeutic modulation

Der NF-κB Signalweg in Melanomzellen und Implikation für seine therapeutische Modulation

by Nadin Pletz
Doctoral thesis
Date of Examination:2012-09-24
Date of issue:2012-12-10
Advisor:Prof. Dr. Michael P. Schön
Referee:Prof. Dr. Michael P. Schön
Referee:Prof. Dr. Matthias Dobbelstein
Referee:Prof. Dr. Jürgen Wienands
Persistent Address: http://dx.doi.org/10.53846/goediss-1487

 

 

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Abstract

English

One of the major challenges in cancer therapy is to overcome drug resistance. Melanoma cells are an illustrative example for this notion, as metastasized melanoma is almost universally resistant against chemotherapy. The NF-κB signaling pathway is constitutively active and plays a crucial role for drug resistance in melanoma cells. This work starts from the observation that doxorubicin leads to profound activation of NF-κB in two different melanoma cell lines, while several other chemotherapeutics with different modes of action did not activate this pathway. Likewise, NF-κB dependent transcription of mediators, which are thought to be involved in tumor progression, was increased by doxorubicin. Notably, the strongest NF-κB activation was detected at a concentration of 1
Keywords: melanoma; chemoresistance; NF-κB; ATM; IKKα; IKKβ; NF-κB inhibition
Schlagwörter: Melanom; Chemoresitenz; NF-κB; ATM; IKKα; IKKβ; NF-κB-Inhibition
 
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