Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway.
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.
Mesh Terms:
Animals, Base Sequence, Binding Sites, Breast Neoplasms, CHO Cells, Cell Line, Tumor, Cell Nucleus, Cell Survival, Chromatin Immunoprecipitation, Cricetinae, Cricetulus, DNA-Binding Proteins, Drug Synergism, Epidermal Growth Factor, Female, Gene Expression, Gene Expression Regulation, Neoplastic, Genes, bcl-1, Genes, fos, HeLa Cells, Humans, Janus Kinase 2, Microscopy, Fluorescence, Microscopy, Immunoelectron, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phosphorylation, Prognosis, Promoter Regions, Genetic, Protein Binding, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, S-Nitroso-N-Acetylpenicillamine, STAT3 Transcription Factor, Signal Transduction, Survival Analysis, Trans-Activators
Animals, Base Sequence, Binding Sites, Breast Neoplasms, CHO Cells, Cell Line, Tumor, Cell Nucleus, Cell Survival, Chromatin Immunoprecipitation, Cricetinae, Cricetulus, DNA-Binding Proteins, Drug Synergism, Epidermal Growth Factor, Female, Gene Expression, Gene Expression Regulation, Neoplastic, Genes, bcl-1, Genes, fos, HeLa Cells, Humans, Janus Kinase 2, Microscopy, Fluorescence, Microscopy, Immunoelectron, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phosphorylation, Prognosis, Promoter Regions, Genetic, Protein Binding, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, S-Nitroso-N-Acetylpenicillamine, STAT3 Transcription Factor, Signal Transduction, Survival Analysis, Trans-Activators
Cancer Cell
Date: Jun. 01, 2005
PubMed ID: 15950906
View in: Pubmed Google Scholar
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