Forced Involution of the Functionally Differentiated Mammary Gland by Overexpression of the Pro-Apoptotic Protein Bax

作者：Rucker Edmund B III^*; Hale Amber N; Durtschi David C; Sakamoto Kazuhito; Wagner Kay Uwe

来源：Genesis, 2011, 49(1): 24-35.

DOI：10.1002/dvg.20691

• mammary gland
• epithelium
• Bax
• apoptosis
• involution
• lactation

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 49:24-35,2011.

• 出版日期2011-1