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c‐myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3
Author(s) -
Sutherland Kate D,
Vaillant François,
Alexander Warren S,
Wintermantel Tim M,
Forrest Natasha C,
Holroyd Sheridan L,
McManus Edward J,
Schutz Gunther,
Watson Christine J,
Chodosh Lewis A,
Lindeman Geoffrey J,
Visvader Jane E
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601455
Subject(s) - biology , mediator , involution (esoterism) , apoptosis , microbiology and biotechnology , mammary gland , socs3 , cancer research , endocrinology , genetics , neuroscience , stat3 , cancer , breast cancer , consciousness
Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine‐mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3 ‐deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c‐myc. Moreover, induction of c‐myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c‐myc target genes, E2F‐1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro‐apoptotic pathways that act in the developing mammary gland and provide evidence that c‐myc regulates apoptosis during involution.