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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.

Pubmed ID: 15950906

Authors

  • Lo HW
  • Hsu SC
  • Ali-Seyed M
  • Gunduz M
  • Xia W
  • Wei Y
  • Bartholomeusz G
  • Shih JY
  • Hung MC

Journal

Cancer cell

Publication Data

June 13, 2005

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

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