Forced involution of the functionally differentiated mammary gland by overexpression of the pro-apoptotic protein bax

Edmund B. Rucker, Amber N. Hale, David C. Durtschi, Kazuhito Sakamoto, Kay Uwe Wagner

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The mammary gland is a developmentally dynamic, hormone-responsive organ that undergoes proliferation and differentiation within the secretory epithelial compartment during pregnancy. The epithelia are maintained by pro-survival signals (e.g., Stat5, Akt1) during lactation, but undergo apoptosis during involution through inactivation of cell survival pathways and upregulation of pro-apoptotic proteins. To assess if the survival signals in the functionally differentiated mammary epithelial cells can override a pro-apoptotic signal, we generated transgenic mice that express Bax under the whey acidic protein (WAP) promoter. WAP-Bax females exhibited a lactation defect and were unable to nourish their offspring. Mammary glands demonstrated: (1) a reduction in epithelial content, (2) hallmark signs of mitochondria-mediated cell death, (3) an increase in apoptotic cells by TUNEL assay, and (4) precocious Stat3 activation. This suggests that upregulation of a single pro-apoptotic factor of the Bcl-2 family is sufficient to initiate apoptosis of functionally differentiated mammary epithelial cells in vivo. genesis, 2011.

Original languageEnglish (US)
Pages (from-to)24-35
Number of pages12
JournalGenesis
Volume49
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Apoptosis
  • Bax
  • Epithelium
  • Involution
  • Lactation
  • Mammary gland

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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