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

Genesis. 2011 Jan;49(1):24-35. doi: 10.1002/dvg.20691. Epub 2011 Jan 3.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Epithelial Cells / physiology
  • Female
  • Genetic Vectors
  • Immunohistochemistry
  • Lactation / genetics
  • Mammary Glands, Animal / embryology*
  • Mammary Glands, Animal / physiology
  • Mice
  • Mice, Transgenic
  • Milk Proteins / genetics
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT5 Transcription Factor / metabolism
  • Up-Regulation / genetics
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*


  • Milk Proteins
  • STAT5 Transcription Factor
  • bcl-2-Associated X Protein
  • whey acidic proteins
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt