Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2

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Shao-Chun Wang1, Huang-Chun Lien, Weiya Xia

  • 1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Cancer Cell
|September 24, 2004
PubMed

Insights

Human epidermal growth factor receptor 2 (HER-2) is found in the cell nucleus, not just the membrane. Nuclear HER-2 regulates gene transcription, including the COX-2 gene, revealing a new role for this cancer-associated protein.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Pathological expression of human ErbB-2 (HER-2) is prevalent in various cancers.
  • HER-2, a member of the EGF receptor tyrosine kinase family, is primarily studied as a cell membrane signaling molecule.

Purpose of the Study:

  • To investigate the subcellular localization of ErbB-2 beyond the cell membrane.
  • To determine if ErbB-2 has a role in nuclear functions, specifically gene regulation.

Main Methods:

  • Immunofluorescence and Western blotting to detect ErbB-2 in cultured cells and tumor tissues.
  • Chromatin immunoprecipitation (ChIP) assays to identify in vivo genomic targets of nuclear ErbB-2.
  • Reporter gene assays to assess the transcriptional activity regulated by ErbB-2.

Main Results:

  • ErbB-2 expression was confirmed in the nucleus of cultured cells and primary tumor tissues.
  • Nuclear ErbB-2 was found to bind to specific genomic regions, including the promoter of the cyclooxygenase-2 (COX-2) gene.
  • ErbB-2 binding to the COX-2 promoter stimulated gene transcription.

Conclusions:

  • This study demonstrates that ErbB-2 is present and functional within the cell nucleus.
  • ErbB-2 acts as a transcriptional regulator, influencing the expression of genes such as COX-2.
  • The nuclear function of ErbB-2 opens new avenues for understanding its role in cancer development and progression.

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