Fig. 4
From: Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid
Summary of DNA damage-induced breast cancer by estrogen and stressors. Stressors induced stress hormones such as catecholamines and glucocorticoids, and these.stress hormones are recognized by each receptor, adrenaline receptor (AR) and glucocorticoid receptor (GR). These receptors activate the downstream pathways. AR stimulate the Gs/protein kinase A (PKA) pathway and phosphoinositide 3-kinase (PI3K)/Akt-mediated murine double minute 2 (MDM2), leading to p53 ubiquitination and degradation [11]. GR regulates the expression of factors critical for DNA damage signaling; Chek1 (Chk1), Chk2, cell division cycle 25 (Cdc25), and Rad9 [77]. Estrogen metabolites and noradrenaline induced DNA damage with Ataxia telangiectasia mutated (ATM) activation [27, 85]. The activation of these pathways leads to DNA damage, and accumulation of DNA damages result in induction of breast cancer