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Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway.

Cancer cell | Jun 13, 2005

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.

Pubmed ID: 15950906 RIS Download

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

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Associated grants

  • Agency: NCI NIH HHS, Id: CA 09299
  • Agency: NCI NIH HHS, Id: CA16672
  • Agency: NCI NIH HHS, Id: P0-1 CA99031
  • Agency: NCI NIH HHS, Id: P20 CA101936
  • Agency: PHS HHS, Id: P50 83639
  • Agency: NCI NIH HHS, Id: R0-1 CA109311

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