Document Type

Article

Publication Date

2002

Abstract

In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4) inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS)-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6) are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a full-length STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4- mediated growth inhibition and induction of apoptosis in human breast cancer cells.

Publication Title

Neoplasia

Volume

4

Issue

4

First Page

324

Last Page

331

Comments

This article was published in Neoplasia, Volume 4, Issue 4, Pages 324-331.

The published version is available at http://dx.doi.org/10.1038/sj.neo.7900248.

Copyright © 2002 The Authors and CC-BY-ND.

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