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Differential function of STAT5 isoforms in head and neck cancer growth control

Oncogene volume 21, pages 2846–2853 (2002)Cite this article

Abstract

Up-regulation of the epidermal growth factor receptor (EGFR) is critical for the loss of growth control in a variety of human cancers, including squamous cell carcinoma of the head and neck (SCCHN). Stimulation of EGFR results in activation of mitogenic signaling pathways including Signal Transducers and Activators of Transcription (STATs). Stat5 activation has been primarily demonstrated in hematopoietic malignancies. Gene disruption studies suggest potentially distinct functions of the Stat5 isoforms, Stat5a and Stat5b, which are encoded by two genes closely linked on human chromosome 17. To determine the function of Stat5 in SCCHN growth control, we studied the expression and constitutive activation of Stat5a and Stat5b in normal and transformed human squamous epithelial cells. Increased constitutive activation of Stat5 was detected in transformed compared with normal squamous cells. Blockade of TGF-α or EGFR, abrogated Stat5 activation. Targeting of Stat5b using antisense oligonucleotides inhibited SCCHN growth. In addition, SCCHN cells stably transfected with dominant negative mutant Stat5b failed to proliferate in vitro. In contrast, targeting of Stat5a using either antisense or dominant negative strategies had no effect on cell growth. These results suggest that TGF-α/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat5b but not Stat5a.

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Acknowledgements

This work was supported by National Institutes of Health grant CA77308 (to JR Grandis).

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Authors and Affiliations

  1. Department of Otolaryngology, The University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

    Paul L Leong, Sichuan Xi, Stephanie D Drenning, Kevin F Dyer, Abbey L Wentzel & Jennifer Rubin Grandis

  2. Department of Pharmacology, The University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

    Jennifer Rubin Grandis

  3. Department of Molecular Genetics and Biochemistry, The University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

    Edwina C Lerner & Thomas E Smithgall

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  1. Paul L Leong
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  2. Sichuan Xi
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Correspondence to Jennifer Rubin Grandis.

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Leong, P., Xi, S., Drenning, S. et al. Differential function of STAT5 isoforms in head and neck cancer growth control. Oncogene 21, 2846–2853 (2002). https://doi.org/10.1038/sj.onc.1205385

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