2002 ASCB Annual Meeting Press Book - page 7

December 14-18, 2002, San Francisco, CA
A Pregnancy-Induced Stem
Cell: Is It the Clue to
The baby may seem the
prime beneficiary but a
mother’s milk has an unex-
pected benefit for the mother.
Studies have shown that early
pregnancy confers a lifelong,
two-fold reduction in breast cancer risk in women regardless
of race, creed, or nationality. Mice and rats also enjoy this
increased protection against mammary cancer even when chal-
lenged with cancer-inducing chemicals.
The biological problem is how. It was commonly held
that all milk-producing breast cells were lost when nursing
stops and that the gland reverts to its virginal state. But if
these parous (i.e. breeding) females no longer have their dis-
tinctive milk-producing cells, where does their anti-cancer
protection come from? The common theory, it turns out, is
wrong. Gil Smith and his colleagues at the National Cancer
Institute in Bethesda, Maryland, in collaboration with Dr. Kay-
Uwe Wagner at the Eppley Cancer Center in Omaha, Nebraska,
have discovered a new pregnancy-induced epithelial cell
population present in the mammary glands of parous mice.
This discovery could help unlock their anti-cancer protective
mechanism, possibly for all women.
Instead of dying out completely, a proportion of milk-
producing cells survive cell death after lactation and the re-
version to pre-pregnancy conditions, say the researchers. With
subsequent pregnancies, the proportion of surviving cells in-
creases within the glands.
Similar cells were not found
in females that were never
pregnant (nulliparous). There-
fore, says Smith and col-
leagues, the mammary cell
population in breeding ani-
mals is fundamentally differ-
ent than those in virgin fe-
This new pregnancy–
dependent epithelial popula-
tion was found in the mammary glands of mice by using a
reporter gene that could be triggered only by the expression
of a milk protein gene. The cells thus identified were isolated
and grown in culture so they could be transplanted into epi-
thelium-free mammary fat. There, the pregnancy-induced
mammary cells acted like stem cells, multiplying and differ-
entiating into most, if not all, of the epithelial subtypes recog-
nized in the gland. Now the question becomes, how do these
pregnancy-induced stem cells protect women when they are
no longer pregnant? This raises the possibility of a common
mechanism to protect all women against breast cancer.
Contact: Gilbert H. Smith, National Cancer Institute, NIH,
MBTL, CCR, Bldg10, Room 5B56, 9000 Rockville Pike,
Bethesda, MD 20892, (301) 496-2385,
Identifying Multilineage Mammary Epithelial Progenitors, In
G. H. Smith,
K. Wagner,
and C. Boulanger
NIH, Bethesda, MD,
Eppley Institute, University of Nebraska,
Omaha, NE,
NCI, NIH, Bethesda, MD
At the ASCB meeting: Presentation 2352, Minisymposium
26: Stem Cells. Author presents: Wednesday, December 18,
2002, 3:45 —4:05 PM.
To follow undifferentiated epithelial cells through lactogenesis (see
diagram), Smith and colleagues used female mice with two transgenes,
WAP-Cre to report cell differentiation and Rosa-lox-LacZ to monitor cell
survival. After lactation ends, fully differentiated, milk-producing aveolar
cells undergo apoptosis as the mammary gland involutes to its virgin state.
It was thought that all aveolar precursors perished as well. Instead, the
reporter genes showed the survival of a new type of pregnancy-induced
epithelial stem cell. Early in pregnancy (top left), the reporter genes show
under blue stain in mammary tissue section. Yet even after involution,
blue stain in small ducts shows the survival (left) of aveolar precursor cells.
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