Delayed involution of the mammary epithelium in BALB/c-p53null mice

In mammals, weaning of neonates and subsequent milk stasis initiates removal of the secretory epithelium of the mammary gland by apoptosis, The p53 tumor suppressor gene is induced rapidly following weaning of neonates, but its role in the process of involution has not been defined. Therefore, experiments were performed to identify the cell types in which the p53 gene is expressed during involution and determine the consequences of its absence in BALB/c-p53(null) mice. Both p53 mRNA and protein were detected in the mammary epithelium within 48 h following meaning and resulted in an eightfold increase in levels of p21(WAF1) mRNA, Induction of p21(WAF1) mRNA was absent in BALB/c-p53(null) mice, and therefore, was shown to be p53-dependent, The BALB/c-p53(null) mice exhibited delayed involution of the mammary epithelium, as measured by 60% greater epithelial area compared to BALB/c-p53(wt) mice through 5 days postweaning, The delay was transient with no differences being apparent at 7 days post-weaning. Expression of the stromal protease stromelysin-1 was unaffected by the absence of p53 suggesting that stromal responses were intact. These data demonstrate that p53 participates in the first stage of involution initiated by the epithelium itself, but does not affect the second phase during which stromal proteases are induced.