Hormone-Induced Protection of Mammary Tumorigenesisin Genetically Engineered Mouse Models - Genetic Engineering: Recent Developments in Applications - page 269

in uncontrolled cancer cell growth. The protein product of the Her-2/neu gene
is overexpressed in 25 to 30% of human breast cancers. A significant proportion
of human intraductal breast carcinomas (ductal carcinoma in situ) demonstrate
Her-2/neu amplification/overexpression, suggesting that the functional activity
of this oncogene is enhanced early in the progression of malignant breast disease.
Virgin activated Her-2/neu transgenic mice have a 100% incidence of mammary
cancer and a high multiplicity of mammary cancers [14,15]. A full-term preg-
nancy does not increase the incidence or multiplicity of mammary adenocarcino-
mas in the activated neu transgenic mice but does decrease the size and metastatic
potential of the mammary tumors in the activated neu transgenic mice [16]. As
these two models mimic many features of major subsets of human breast cancer,
we tested whether a short-term exposure to estrogen and progesterone (p53-null
and MMTV-neu models) or just estrogen (MMTV-neu model) would induce a
protective effect on spontaneous tumorigenesis.
Materials and Methods
Mice
BALB/c mice were bred and maintained at Baylor College of Medicine. The do-
nor mice were BALB/c p53 homozygous null, and the recipient mice were p53
wild type. FVB (activated neu) mice were bred and maintained at the Cancer
Research Laboratory, University of California, Berkeley, California, and at Texas
Tech University of Health Sciences Center, El Paso, Texas. All mice were main-
tained in conventional mouse facilities with food and water provided ad libitum,
and the room temperature was set at 70°F (21°C). The animal facilities at Baylor
College of Medicine and University of California are accredited by the American
Association of Laboratory Animal Care. All experiments followed NIH guidelines
for the care and use of mice.
p53-null Model
The basic transplantation protocol for the experiments using the p53-null model
was as described [10]. In brief, fragments of mammary ducts from 8 to 10-week-
old female p53-null mice were transplanted into the cleared mammary fat pads of
3-week-old or 11-week-old female mice. Although the p53 deletion is the same
in all donor mice, the array of secondary alterations important for neoplastic
development include both common and unique events. The consequence is that
the tumorigenic capabilities of mammary gland fragments vary over a small range
between donor mice in the same host environment. Thus, the time to palpable