Dual signaling mechanisms of estrogen: Phosphorylation of P53 at Ser15 in aging HMEC in the absence of estrogen receptor

Abstract

AbstractPrimary cultures of human mammary epithelial cells (HMEC) ex vivo underwent significant morphological and functional changes during the process of aging. Cells in S phase significantly declined after 19 d and accumulated in G0/G1 and G2/M phase after 50 d. Simultaneously, the initial estrogen receptor expression of 32,3% dropped to less than 1% in 19 d and 50 d aged HMEC, respectively. Estrogen treatment of HMEC demonstrated unaltered levels of P53 and phosphorylated P53 after 60 min. After 24 h of estrogen treatment, however, Western blot analysis revealed a significantly enhanced phosphorylation of P53 at Ser15 in 5 d and 19 d HMEC populations, respectively. A phospho‐P53 ELISA confirmed a significant Ser15‐phosphorylation of P53 in both HMEC populations following 24 h of estrogen stimulation, but no significant changes after 60 min, respectively. According to the estrogen receptor depletion in 19 d aged HMEC, these data indicated a receptor‐independent estrogen signaling.