[PDF][PDF] Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway

HW Lo, SC Hsu, M Ali-Seyed, M Gunduz, W Xia, Y Wei… - Cancer cell, 2005 - cell.com
HW Lo, SC Hsu, M Ali-Seyed, M Gunduz, W Xia, Y Wei, G Bartholomeusz, JY Shih
Cancer cell, 2005cell.com
Epidermal growth factor receptor (EGFR) exists in the nucleus of highly proliferative cells
where it functions as a transcription factor. Although EGFR has transactivational activity, it
lacks a DNA binding domain and, therefore, may require a DNA binding transcription
cofactor for its transcriptional function. Here, we report that EGFR physically interacts with
signal transducers and activators of transcription 3 (STAT3) in the nucleus, leading to
transcriptional activation of inducible nitric oxide synthase (iNOS). In breast carcinomas …
Summary
Epidermal growth factor receptor (EGFR) exists in the nucleus of highly proliferative cells where it functions as a transcription factor. Although EGFR has transactivational activity, it lacks a DNA binding domain and, therefore, may require a DNA binding transcription cofactor for its transcriptional function. Here, we report that EGFR physically interacts with signal transducers and activators of transcription 3 (STAT3) in the nucleus, leading to transcriptional activation of inducible nitric oxide synthase (iNOS). In breast carcinomas, nuclear EGFR positively correlates with iNOS. This study describes a mode of transcriptional control involving cooperated efforts of STAT3 and nuclear EGFR. Our work suggests that the deregulated iNOS/NO pathway may partly contribute to the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3.
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