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Cell signals shed light on breast cancer
A key signal that triggers breast stem cells to grow has been identified, helping scientists to understand better how breast cancer develops.

The research, by Associate Professor Jane Visvader of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne and colleagues, report their findings online today ahead of print in the journal Nature.

"What's exciting is that it helps spotlight some of the mechanisms that may be involved in very early stages of breast cancer," says co-author, Associate Professor Geoffrey Lindeman, of WEHI.

"By identifying the signals, it might help highlight some of the methods that could be used to help either treat, or perhaps even better, prevent, breast cancers."

The female hormones progesterone and oestrogen are involved in the development of normal breasts, and in the development of breast cancer.

But researchers have noticed that increased exposure to these hormones, for example through early periods, late menopause, hormone replacement therapy, or, in the short term, pregnancy, can increase the risk of breast cancer.

Until now, scientists haven't been sure which cells were involved in breast cancer, but breast stem cells have been suspected because they are long-lived and probably have time to develop the mutations linked to cancer, says Lindeman.

But he and colleagues previously discovered that breast stem cells in mice and humans do not have receptors, or sensors, for progesterone and oestrogen.

So how could hormones affect these cells?
'Exquisitely sensitive'

For this latest study, post-doctoral researcher, Dr Marie-Liesse Asselin-Labat, carried out laboratory research on mouse mammary stem cells (MaSCs), which Lindeman says bear a "striking resemblance" to human breast stem cells.

The study found that MaSCs are highly responsive to steroid hormone signalling.

"Despite lacking the sensors [for oestrogen and progesterone], the stem cell is exquisitely sensitive to hormone manipulation," says Lindeman.

In the study, the number of MaSCs increased with pregnancy, and with oestrogen and progesterone treatment, but decreased when ovaries were removed, or anti-oestrogen treatments were given.
'Middle-men'

Lindeman says one of the study's key findings is that cells that line the breast ducts play a kind of "middle man" role between the hormones and the stem cells.

He says these cells, which have oestrogen and progesterone sensors, respond to the hormones, and then release a chemical signal, called RANK, which tells the MaSCs what to do.

"There seems to be this cross talk or conversation that goes on between hormone-sensor-positive cells in the breast and the stem cells," says Lindeman.

He says the findings will help scientists researching drugs to prevent and treat breast cancer.

RANK has previously been linked to breast cancer and trials are currently underway to see if drugs that inhibit RANK will prevent breast cancer from spreading to the bone.

"Our findings suggest they might also be helpful to prevent breast cancer," he says.

Lindeman says women who have their ovaries removed [these produce oestrogen and progesterone] or take anti-oestrogen therapy can lower their risk of breast cancer.

But the problem with this is that such interventions can have side-effects such as hot flushes, mood swings, vaginal dryness and osteoporosis.

He says more targeted treatments that interfere with signals like RANK would hopefully reduce breast cancer risk without such side-effects.

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