The epidermal growth factor receptor gene is highly regulated and responsive to extracellular stimuli that control cell growth. We have identified five putative nuclear factor-κB (NF-κB) binding sites within the epidermal growth factor receptor (EGFR) promoter region by sequence analysis. We have analyzed the potential role of NF-κB family members in the regulation of the EGFR transcription. Electrophoretic mobility shift analysis demonstrated that the p50 and p49, subunit proteins of the NF-κB, bound to the EGFR promoter at four out of five of these sites. However, it was found that NF-κB could not transactivate the EGFR by cotransfection experiments with each NF-κB subunit, using p50, p65 and c-Rel and an EGFR promoter luciferase reporter. Treatment of cells with tumor necrosis factor (TNF)-α, which could degrade the I-κB and then result in translocation of NF-κB to nucleus, did not enhance EGFR promoter reporter gene transcription. Also, TNF-α did not induce EGFR expression at the protein level. These results indicate that even though purified NF-κB can bind to the putative sites, there is no evidence that NF-κB transactivates the EGFR promoter region.

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