The Influence Of The Epidermal Growth Factor Receptor On The DNA Damage Response As Examined Through Clathrin Affiliated Signalling Complexes

Abstract

The EGFR is an oncogene that when dysregulated, can cause tumour progression. Upon binding ligand, EGFR triggers activation of many signalling pathways including PI3K/Akt, RasErk, STAT, and PLCγ1. EGFR may also control DNA repair mechanism, although this remains poorly understood. Control of DNA repair by EGFR may be particularly relevant in the context of action and resistance of cancer drugs that cause DNA damage (eg. Cisplatin). I have examined how acute activation (10-30 minutes) of EGFR regulates DNA repair induced by cisplatin treatments and by examination of repair-markers such as γH2AX. I observed that as little as 10 minutes of EGF stimulation is sufficient to elicit remodelling of γH2AX in chronic cisplatin-treated cells. Using these methods, I dissected the EGFR signals and membrane traffic phenomena required for EGFR-dependent control of DNA repair. This work may reveal new ways to enhance the efficacy of existing chemotherapies, such as cisplatin, for cancer treatment.