Linear and cooperative signaling: roles for Stat proteins in the regulation of cell survival and apoptosis in the mammary epithelium

The mammary epithelium undergoes cyclical periods of cellular proliferation , differentiation and regression. These processes are under the control of the hormones secreted during pregnancy, lactation and involution. Signaling pathways have been identified that connect the hormonal stimuli with the t ranscription of genes responsible for the determination of the cellular fat e. The kinetics of induction and deinduction have suggested that cytokine-a ctivated Stat proteins play a crucial role. Stat5 is strongly activated tow ards the end of pregnancy, persists in an activated state during pregnancy and is rapidly inactivated after cessation of suckling. Stat3 activation is hardly detectable during lactation, but is strongly induced at the onset o f involution. The phenotypes of mice in which these genes have been inactiv ated through homologous recombination corroborate some of the functional as signments deducted from the activation pattern. Stat3 activation seems to b e a driving force in the induction of apoptosis early in the involution per iod.