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Constitutive activation of Stat5b contributes to carcinogenesis in vivo

Sichuan Xi1, Qing Zhang, William E Gooding

  • 1Departments of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Cancer Research
|October 30, 2003
PubMed

Insights

Signal transducers and activators of transcription (STAT) proteins are crucial in cancer. Stat5b activation contributes to head and neck squamous cell carcinoma development and may be a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Effective solid tumor treatment strategies are hindered by a lack of understanding of carcinogenesis pathways.
  • Signal transducers and activators of transcription (STAT) proteins are implicated in tumor progression, but distinct roles for Stat5a and Stat5b in epithelial cancers remain unclear.

Purpose of the Study:

  • To investigate the roles of Stat5a and Stat5b isoforms in head and neck squamous cell carcinoma (HNSCC).
  • To determine if Stat5b activation is a potential therapeutic target in HNSCC.

Main Methods:

  • Analysis of Stat5a/b expression and activation in human HNSCC tissues and a xenograft model.
  • Selective blockade of Stat5a/b and epidermal growth factor receptor (EGFR) using antisense oligonucleotides in a xenograft model.
  • Correlation of Stat5 activation levels with tumor progression in patient tissues.

Main Results:

  • Blockade of Stat5b, but not Stat5a, inhibited tumor growth and Stat5 target gene expression in vivo.
  • Epidermal growth factor receptor blockade partially abrogated Stat5 activation, indicating a link between EGFR and Stat5.
  • Increased Stat5b expression and phosphorylation were observed in HNSCC tumors compared to normal epithelium, correlating with malignant progression.

Conclusions:

  • Constitutive activation of Stat5b plays a significant role in squamous cell tumorigenesis of the head and neck.
  • Stat5b activation is a potential therapeutic target for HNSCC.

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