Hormone-Induced Protection of Mammary Tumorigenesisin Genetically Engineered Mouse Models - Genetic Engineering: Recent Developments in Applications - page 276

host is shown in Figure 4 and Table 1. The tumorigenic capability was the same
whether the target epithelial cells were directly exposed to estrogen/progesterone
or transplanted into an estrogen/progesterone-treated host environment (3/15
versus 4/20, respectively; p > 0.05). The tumorigenic response was decreased from
45% (18/40 combined controls) to 20% (7/35 combined treatment; p < 0.05).
Figure 4. The effect of hormone-induced systemic changes on tumorigenesis in p53-null mammary epithelial
transplants. Mammary epithelial transplants in a host exposed to estradiol and progesterone before transplantation
(open triangles and dot-dashed line) also had a significant decrease in tumor incidence (p < 0.05) compared
with mice not exposed to the hormones (filled triangles and broken line). The flow diagrams illustrate the
experimental treatment plans.
The proliferative state of the mammary epithelial cells was assessed at 4 to 12
weeks after removal of the hormones in all three experiments (Figures 5 and 6).
In experiment 1, at 4 and 8 weeks after hormone removal, the control transplants
showed a BrdU-labeling index of 9.8 and 8.2, respectively, in comparison with
1.5 and 1.8, respectively, in the hormone-treated transplants (p < 0.05). In experi-
ment 2, at 4 weeks after hormone removal (that is, 26 weeks after transplantation),
the control transplants showed a BrdU-labeling index of 19.8 in comparison with
7.8 in the hormone-treated transplants (p < 0.05). In experiment 3, at 12 weeks
after hormone removal (that is, 8 weeks after transplantation into 11-week-old
mice), the control transplants had a BrdU-labeling index of 9.5 in comparison
with 4.5 in the transplants in the hormone-treated mice (p < 0.05).