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New clues to why older women are more vulnerable to breast cancer
Date:6/5/2014

tissue from young women was placed on a soft polymer, multipotent progenitors differentiated into milk-producing luminal cells. When the tissue was placed on a stiff polymer, the cells reduced the production of luminal cells and ramped up the production of tumor-fighting myoepithelial cells.

"We think this is a defense mechanism. The epithelia tissue recognizes that stiffness isn't good and produces tumor suppressants," says LaBarge.

But this defense wasn't observed in tissue from women older than 55. Instead of responding to a stiff polymer by upping the production of tumor-suppressing cells, multipotent progenitors from older women produced equal amounts of luminal and tumor-suppressing cells. They also made more of themselves. That's bad for a couple of reasons. The majority of cancers diagnosed in older women are luminal, and more multipotent progenitors means more cells that can become cancerous.

"We found that as women age, multipotent progenitors, which are the cells responsible for maintaining healthy homeostasis in breast tissue, no longer respond to their microenvironment like they do in younger women," says LaBarge.

"Our work shows that one reason for this is that multipotent progenitors in older tissue do not correctly perceive differentiation cues, such as the mechanical stiffness of their surroundings," he adds.

The scientists traced this failure to a breakdown in a cellular process. The process converts external mechanical cues, in this case the stiffness of the tissue outside of the cell membrane, into an internal molecular message that tells the cell nucleus what to do. In multipotent progenitors in women older than 55, the molecules that help deliver this message are inefficiently activated, the scientists found.

They believe this breakdown stems from changes in the way women's genes are activated and silenced as they grow older.

Their functional analysis of multipotent progenitors was
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Contact: Dan Krotz
dakrotz@lbl.gov
510-486-4019
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert

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