Hormones promote stem cell growth

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The Scientist

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Hormones promote stem cell growth

Posted by Scudellari

[Entry posted at 11th April 2010 06:00 PM GMT]

Estrogen and progesterone promote the

proliferation and activity of mouse mammary stem

cells, according to new research published online

today (April 11) at Nature -- possibly explaining

the link between exposure to the hormones and breast cancer.

" It's a pretty good paper, " said

Stingl<http://www.cambridgecancer.org.uk/research/loc/cambridge/ccri/stinglj/?vi\

ew=CRI & source=research>,

a researcher at the Cancer Research UK Cambridge

Research Institute, who did not participate in

the study. In a very direct way, the researchers

have successfully measured the effects of

progesterone and estrogen on mammary stem cells, he said.

Estrogen and progesterone levels have profound

effects on breast development and breast cancer

risk. There is a clear correlation between number

of menstrual cycles (and thus lifetime exposure

to these hormones) and breast cancer risk, for

example, and therapeutic regimens that inhibit

the binding or synthesis of estrogen reduce the

rate of breast cancer recurrence for some

patients by almost half. The mechanism by which

these hormones work, however, remains elusive, said Stingl.

One possible role is their effects on mammary

stem cells (MaSCs), whose highly proliferative

abilities make them suspects as causative agents

in breast cancer. But there was no proof that

MaSCs respond to hormones, Stingl said. And there

was a major theoretical problem: MaSCs lack

receptors for both hormones. The question then

became, is it possible that cells with no

receptors for progesterone or estrogen are still affected by their presence?

To find out, Jane Visvader of the Walter and

Eliza Hall Institute in , Australia, and

her colleagues tested the activity of MaSCs in

the absence of estrogen and progesterone.

Removing the ovaries from young adult mice, the

researchers saw a significant decrease in the

number of mammary stem cells. Conversely,

treating young mice with estrogen and

progesterone pellets to expose them to far

greater levels of hormones than normal, the team

recorded an increase in the number of stem cells.

Together, these results suggest the hormones do indeed promote MaSC growth.

Visvader and her colleagues also assessed the

size of MaSC populations during pregnancy and

found an eleven-fold increase in the number of

stem cells in the mammary glands during

mid-pregnancy -- when females have highly

elevated levels of progesterone -- compared to

glands from virgin mice. The finding coincides

with the observation that women have an increased

risk of developing breast cancer for a short

period following pregnancy. " This increase in the

number of mammary stem cells [during pregnancy]

provides a tantalizing mechanism to account for

that [increased risk], " said Visvader.

One concern is that what the researchers thought

were MaSCs may actually have been other cell

types, said Cathrin

Brisken<http://www.nccr-oncology.ch/scripts/index.aspx?idd=85>,

a breast cancer researcher at the Ecole

Polytechnique Fédérale in Lausanne, Switzerland.

" The paper makes claims that are very reasonable,

but doesn't provide the data for it, " said

Brisken. Accurately identifying and counting

MaSCs requires rigorous assays, she said, and

" one has to be really careful of whether given

markers really identify a stem cell population. "

To address this concern, the researchers injected

the suspected MaSCs into a fat pad to demonstrate

the cells' capacity to grow into new mammary

glands in vivo -- the gold standard for

identifying MaSCs. Additionally, mice exposed to

estrogen and progesterone grew fuller mammary

glands than mice lacking ovaries, demonstrating

increased activity of the transplanted MaSCs in

the presence of the hormones. " The heart of the

paper is the transplants, " Stingl said, " and they've done those. "

But how progesterone and estrogen stimulate MaSC

growth and activity is still unknown. Researchers

suspect the effect occurs through paracrine

signaling: Cells with progesterone and estrogen

receptors sense the hormones, and then release a

signal to the nearby stem cells. Visvader and her

team identified one possible signal, RANKL, a

ligand important for mouse mammary gland

development, that seems to affect MaSC expansion

during pregnancy, but " the whole system is not

quite worked out yet, " said Stingl.

Read more:

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promote stem cell growth - The Scientist -

Magazine of the Life Sciences

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