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

First Author  Rucker EB 3rd Year  2011
Journal  Genesis Volume  49
Issue  1 Pages  24-35
PubMed ID  21254334 Mgi Jnum  J:167975
Mgi Id  MGI:4881563 Doi  10.1002/dvg.20691
Citation  Rucker EB 3rd, et al. (2011) Forced involution of the functionally differentiated mammary gland by overexpression of the pro-apoptotic protein bax. Genesis 49(1):24-35
abstractText  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. (c) 2011 Wiley-Liss, Inc.
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