Selective cell ablation in the mammary gland of transgenic mice

Nitroreductase-mediated cell ablation is very rapid and mediated by a p53-independent apoptotic pathway

“…These morphological changes appeared homogenously throughout the gland in contrast to the CB1954-NTR-mediated effects which showed cell death was patchy reflecting the variegated expression of the BLG-NTR transgene as we have previously reported. 9,18 NTR-CB1954-induced cell apoptosis is p53 independent It has been shown that CB1954 can increase p53 expression in both NTR-transfected cell lines and in the secretory epithelial cells in the mammary gland of BLG-NTR transgenic mice. 18 To investigate whether NTR-CB1954-induced cell apoptosis was p53 dependent, RED 40 mice were crossed with a 'knock-out' mouse strain carrying a p53 null allele 17 and female progeny resulting from two sequent crosses were genotyped by PCR ( Figure 3) and ablation studies were carried out.…”

“…9,18 NTR-CB1954-induced cell apoptosis is p53 independent It has been shown that CB1954 can increase p53 expression in both NTR-transfected cell lines and in the secretory epithelial cells in the mammary gland of BLG-NTR transgenic mice. 18 To investigate whether NTR-CB1954-induced cell apoptosis was p53 dependent, RED 40 mice were crossed with a 'knock-out' mouse strain carrying a p53 null allele 17 and female progeny resulting from two sequent crosses were genotyped by PCR ( Figure 3) and ablation studies were carried out. Extensive cell death was observed in the mammary gland of BLG-NTR transgenic mice after CB1954 treatment irrespective of whether or not they carried a functional p53 gene.…”

“…23 NTR-mediated cell death by CB1954 increases the expression of wild-type p53, both in vitro and in vivo. 18 To understand more fully the mechanism of CB1954-NTR-mediated cell death it is thus essential to know whether p53 is required. By crossing BLG-NTR transgenic mice with a p53-deficient mouse strain we generated a mouse strain which expressed NTR in the luminal cells of the mammary gland during gestation and lactation but lacked functional p53.…”

“…14 The oncosuppressor gene p53 is one of the crucial factors in DNA-damage induced apoptosis. [15][16][17] NTR-CB1954-mediated apoptotic cell death in the mammary gland coincides with an up-regulation of p53 expression 18 raising the question whether or not this process is p53 dependent. P53 dependence would have important implications for any proposed anti-cancer therapy involving NTR-CB1954, since disruption of the p53 gene is the most frequent genetic event associated with human cancer.…”

The normal breast: cancer risk and prevention - an overview

“…A novel method for selective cell ablation in the mammary gland of mice is reported here by Gusterson et al (1997). A novel method for selective cell ablation in the mammary gland of mice is reported here by Gusterson et al (1997).…”