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Forced involution of the functionally differentiated mammary gland by overexpression of the pro‐apoptotic protein bax
Author(s) -
Rucker Edmund B.,
Hale Amber N.,
Durtschi David C.,
Sakamoto Kazuhito,
Wagner KayUwe
Publication year - 2011
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20691
Subject(s) - apoptosis , involution (esoterism) , biology , downregulation and upregulation , mammary gland , microbiology and biotechnology , programmed cell death , lactation , endocrinology , medicine , gene , cancer , consciousness , biochemistry , genetics , neuroscience , breast cancer , pregnancy
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. © 2011 Wiley‐Liss, Inc.