c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3

Kate D. Sutherland, François Vaillant, Warren S. Alexander, Tim M. Wintermantel, Natasha C. Forrest, Sheridan L. Holroyd, Edward J. McManus, Gunther Schutz, Christine J. Watson, Lewis A. Chodosh, Geoffrey J. Lindeman, Jane E. Visvader

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution.

Original languageEnglish (US)
Pages (from-to)5805-5815
Number of pages11
JournalEMBO Journal
Volume25
Issue number24
DOIs
StatePublished - Dec 13 2006

Fingerprint

Human Mammary Glands
Suppressor of Cytokine Signaling Proteins
Tissue
Apoptosis
Phenotype
Breast
Prolactin
myc Genes
Genes
Chemical activation
Cytokines
Weaning
Lactation
Epithelium
Epithelial Cells
Pregnancy

Keywords

  • Apoptosis
  • Mammary
  • Socs3
  • Stat3
  • c-myc

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Sutherland, K. D., Vaillant, F., Alexander, W. S., Wintermantel, T. M., Forrest, N. C., Holroyd, S. L., ... Visvader, J. E. (2006). c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. EMBO Journal, 25(24), 5805-5815. https://doi.org/10.1038/sj.emboj.7601455

c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. / Sutherland, Kate D.; Vaillant, François; Alexander, Warren S.; Wintermantel, Tim M.; Forrest, Natasha C.; Holroyd, Sheridan L.; McManus, Edward J.; Schutz, Gunther; Watson, Christine J.; Chodosh, Lewis A.; Lindeman, Geoffrey J.; Visvader, Jane E.

In: EMBO Journal, Vol. 25, No. 24, 13.12.2006, p. 5805-5815.

Research output: Contribution to journalArticle

Sutherland, KD, Vaillant, F, Alexander, WS, Wintermantel, TM, Forrest, NC, Holroyd, SL, McManus, EJ, Schutz, G, Watson, CJ, Chodosh, LA, Lindeman, GJ & Visvader, JE 2006, 'c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3', EMBO Journal, vol. 25, no. 24, pp. 5805-5815. https://doi.org/10.1038/sj.emboj.7601455
Sutherland KD, Vaillant F, Alexander WS, Wintermantel TM, Forrest NC, Holroyd SL et al. c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. EMBO Journal. 2006 Dec 13;25(24):5805-5815. https://doi.org/10.1038/sj.emboj.7601455
Sutherland, Kate D. ; Vaillant, François ; Alexander, Warren S. ; Wintermantel, Tim M. ; Forrest, Natasha C. ; Holroyd, Sheridan L. ; McManus, Edward J. ; Schutz, Gunther ; Watson, Christine J. ; Chodosh, Lewis A. ; Lindeman, Geoffrey J. ; Visvader, Jane E. / c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. In: EMBO Journal. 2006 ; Vol. 25, No. 24. pp. 5805-5815.
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