Regulation of p53 and its targets during involution of the mammary gland

Post-lactational involution of the mammary gland provides a system in which to study the expression and function of genes that regulate apoptosis in t he context of a normal tissue. The functions of the p53 tumor suppressor ge ne have been extensively studied as a mediator of apoptosis in response to DNA damage, but its regulation in normal physiologic processes has been poo rly characterized. Expression of p53 mRNA was shown to be among the first g enes to be induced in mammary tissue following weaning of neonates. Althoug h involution proceeds in the absence of a functional p53 gene, it is delaye d compared to normal individuals. Therefore, involution can be viewed as bi phasic with initial responses being sensitive to p53, whereas secondary res ponses being p53-independent. These observations can be exploited to determ ine the subset of genes that are p53-responsive and that mediate the effect s of p53 in normal mammary tissue.