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  • Original Paper
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Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2

Oncogene volume 22, pages 3608–3615 (2003)Cite this article

Abstract

The signal transducing protein Stat3 activates gene transcription in cells in response to multiple cytokines. Constitutive activation of Stat3 has been observed in solid tumors including head and neck squamous cell carcinoma. Stat3 activation in cancer has been associated with autocrine stimulatory loops and is believed to convey a growth advantage to cells. We now demonstrate ligand-independent activation of Stat3 by high cell density in multiple cancer cell lines. Activation of Stat3 is associated with antiproliferative rather than proliferative conditions. Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity. Our data supports a model in which Stat3 activity is partially suppressed by cdk2 in growing cells and derepressed upon cell confluence.

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Acknowledgements

We thank John Marshall for ZRP cells, Ora Weiss, and Thomas Kleyman for MDCK cells, James James Johnston for 3T3-SOCS cells, Schlomo Melmed for a SOCS-luciferase construct, Peter Nissley for a GST-SOCS plasmid, Sarah Dunn and Martin Myers for a SOCS3-expression plasmid, Jacqueline Bromberg for a Stat3C expression plasmid, and Steven Dowdy for GFPTat and dominant-negative cdk2Tat plasmids. This work was supported in part by NIH Grants RolHL65172 (RAS), RO1CA77308 (JRG), and an UPCI pilot grant (RAS).

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Authors and Affiliations

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

    Richard A Steinman, Yalin Lu & Christine Stehle

  2. Department of Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, USA

    Abbey Wentzel & Jennifer Rubin Grandis

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  1. Richard A Steinman
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Correspondence to Richard A Steinman.

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Steinman, R., Wentzel, A., Lu, Y. et al. Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2. Oncogene 22, 3608–3615 (2003). https://doi.org/10.1038/sj.onc.1206523

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