STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells

Jennifer L. Gooch, Barbara Christy, Douglas Yee

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68 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)324-331
Number of pages8
Issue number4
StatePublished - 2002

Bibliographical note

Funding Information:
Abbreviations: ERα, estrogen receptor α; IL-4, interleukin-4; IRS, insulin receptor substrate; SFM, serum - free media; STAT, signal transducer and activator of transcription Address all correspondence to: Douglas Yee, MD, MMC 806, 420 Delaware Street SE, Minneapolis, MN 55455, USA. E - mail: 1This work was supported by Public Health Service ( PHS) grant R01CA74285, and PHS Cancer Center Support grant P30CA54174 ( DY ), and DMAD17 - 98 - 1-8339 (JG ). Received 6 December 2001; Accepted 14 February 2002.


  • Apoptosis
  • Breast cancer
  • IL-4
  • Insulin receptor substrate
  • STAT6


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