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A novel cis-acting element in Her2 promoter regulated by Stat3 in mammary cancer cells

Lu Qian1, Liyong Chen, Ming Shi

  • 1Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.

Biochemical and Biophysical Research Communications
|May 16, 2006
PubMed

Insights

Signal transducer and activator of transcription 3 (Stat3) regulates Her2 expression in breast cancer. Constitutively activated Stat3 binds to the Her2 promoter, increasing Her2 mRNA and protein levels.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Signal transducer and activator of transcription 3 (Stat3) is implicated in breast cancer development and oncogenesis.
  • Her2 (Human Epidermal growth factor Receptor 2) is a key protein in breast cancer, and its expression is often dysregulated.

Purpose of the Study:

  • To investigate the role of Stat3 in regulating Her2 expression in breast cancer cells.
  • To identify and characterize a novel cis-acting element in the Her2 promoter involved in Stat3-mediated regulation.

Main Methods:

  • Reporter assays were used to assess the activity of the identified element (Pal2) in the Her2 promoter.
  • Deletion analysis was performed to pinpoint the location of the regulatory element.
  • Chromatin immunoprecipitation (ChIP) assays confirmed the binding of Stat3 to the Her2 promoter.
  • Experiments were conducted in MCF-7 breast cancer cells, some stably expressing constitutively activated Stat3 (Stat3C).

Main Results:

  • A novel palindromic cis-acting element, Pal2 (nucleotides -529 to -505), was identified in the Her2 promoter with repression activity in Her2-low breast cancer cells.
  • The Pal2 sequence (TTAAGATAA) showed homology to the Stat3 binding site.
  • Reporter assays demonstrated that Pal2 is regulated by constitutively activated Stat3 (Stat3C).
  • Stable expression of Stat3C in MCF-7 cells led to increased Her2 mRNA and protein levels, confirming Stat3's stimulatory effect on Her2 expression.
  • ChIP assays confirmed direct binding of Stat3 to the Her2 promoter.

Conclusions:

  • Constitutively activated Stat3 directly regulates Her2 expression in breast cancer cells.
  • The findings highlight a mechanism by which Stat3 influences Her2 expression, potentially impacting breast cancer progression.
  • Further research is warranted to explore the differential effects of Stat3 on breast cancer cells with varying Her2 levels.

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