Hormone-Induced Protection of Mammary Tumorigenesisin Genetically Engineered Mouse Models - Genetic Engineering: Recent Developments in Applications - page 274

outgrowth morphology. The outgrowths exhibited normal alveolar differentiation
to 2 weeks of estrogen/progesterone exposure at 4 weeks after transplantation. At
8 to 12 weeks after transplantation, the outgrowths appeared as normal mammary
duct arborization with no evidence of ductal hyperplasia (Figure 2). However,
whole-mount analysis of the glands at 45 weeks after transplantation revealed
extensive ductal hyperplasia in both control and hormone-treated glands. Prema-
lignant lesions were present in 13/31 glands in the estrogen/progesterone-treated
group (42%) and 6/13 glands in the untreated controls (46%) (Figure 2; p >
0.05). These data suggest that hormones act to block premalignant progression
and not the onset of hyperplastic growth.
Figure 2. Effect of short-term hormone treatment on gland morphology in p53-null transplants. (a,b) Mammary
whole mounts were prepared 4 weeks after the removal of hormones in mice from experiment 1A. The ductal
organization at the histological and microscopic (hematoxylin/eosin-stained sections, not shown) was similar
in the untreated (a) and treated (b) mice (original magnification ×2). (c-f ) Whole mounts were prepared at
45 weeks after transplantation in transplants that had not yet developed palpable tumors. A large number of
transplants in the untreated group (46%) (original magnifications ×1 (c) and ×2 (d)) and in the treated group
(42%) (original magnifications ×1 (e) and ×2 (f )) contained areas of ductal hyperplasias (arrows).
effect of developmental state on tumorigenesis in P53-null
Mammary epithelium
The tumorigenic response of the mammary epithelium exposed to estrogen and
progesterone combination at 23 to 25 weeks after transplantation is shown in