The regulation of annexin-A1's expression and function(s) by 17-Beta-Estradiol in MCF7 Breast cancer cells

Abstract

Both estrogen and Annexin-A1 (Anx-A1) have been implicated in breast cancer and are also able to regulate the mitogen-activated protein kinase/ extracellular signal-regulated kinase (MAPK/ERK) pathway. We hence hypothesize that estrogen (17-beta-estradiol/E2) may induce the expression of Anx-A1 for the regulation of cell proliferation via the MAPK signaling pathway. We show that prolonged exposure of cells to high physiological levels of E2 led to an up-regulation of Anx-A1 expression and a corresponding inhibition of cell proliferation. In addition, Anx-A1 had direct anti-proliferative effects on cells, possibly via a constitutive over-activation of ERK. Finally, the anti-proliferative role of Anx-A1 was directly responsible for the reduced proliferation rates observed when cells were exposed to high E2 concentrations for an extended time period. We thus believe that Anx-A1 may act as a tumor suppressor in cells and that its expression could be increased, when needed, to put a brake on uncontrolled cellular proliferation.