Constitutive Activation of Stat5b Contributes to Carcinogenesis in Vivo

Sichuan Xi, Qing Zhang, William E. Gooding, Thomas E. Smithgall, Jennifer Rubin Grandis

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

The development of more effective prevention and treatment strategies for solid tumors is limited by an incomplete understanding of the critical growth pathways that are activated in carcinogenesis. Signal transducers and activators of transcription (STAT) proteins have been linked to transformation and tumor progression. Studies to date have not elucidated clear and distinct roles for Stat5 genes (Stat5a and Stat5b) in human epithelial cancers. We analyzed the role of Stat5a/b isoforms in squamous cell carcinoma of the bead and neck using expression and activation studies in human tissues and in a xenograft model after selective targeting. In a xenograft model, blockade of Stat5b, but not Stat5a, using antisense oligonucleotides resulted in tumor growth inhibition and abrogation of Stat5 target genes in vivo. Blockade of the epidermal growth factor receptor resulted in partial abrogation of Stat5 activation, thus linking epidermal growth factor receptor to Stat5 in vivo. In tissues from 33 individuals with head and neck cancer, Stat5 activation levels were correlated with progression to a malignant phenotype, where increased expression and phosphorylation of Stat5b were detected consistently in tumors compared with their epithelial counterparts. Thus, constitutive activation of Stat5b contributes to squamous cell tumorigenesis and may serve as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)6763-6771
Number of pages9
JournalCancer research
Volume63
Issue number20
StatePublished - Oct 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Xi, S., Zhang, Q., Gooding, W. E., Smithgall, T. E., & Grandis, J. R. (2003). Constitutive Activation of Stat5b Contributes to Carcinogenesis in Vivo. Cancer research, 63(20), 6763-6771.