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CSHL scientists show how a protein that determines cell polarity prevents breast cancer
Date:11/26/2008

plastic dishes as an experimental platform. "Such models have been quite satisfactory in allowing scientists to analyze mechanisms involved in cell growth" says Muthuswamy. But they don't allow scientists to capture the three-dimensional organization of cells seen in tissue, including their polarity. A major enabler for Muthuswamy's current work is an experimental model system that enables him to grow breast cells in three-dimensional cultures to allow them to form structures similar to those seen in breast ducts and lobules.

On Muthuswamy's novel test bed, cells undergo morphogenesis --a growth/death cycle that expands and shapes tissue. Such cells give rise to what looks like a hollow ball of cells. The polarity protein Scribble lines the sides of each cell, lending to each a specific orientation.

What happens when Scribble is missing

In breast epithelial cells grown in this new experimental culture system, when the Scribble protein is missing, cells were observed by Muthuswamy's team to radically change their character and behavior. They lost their orientation -- an effect one might have predicted since Scribble regulates polarity -- and started to fill the hollow ball.. The team hypothesized that the filling-in of the "ball" was akin to the process, in living creatures, by which a breast epithelial tumor would form.

To test this notion, the experiment was moved from a cell-culture dish to living animals. Mouse breasts were generated using genetically engineered cells that had stopped producing the Scribble protein. In such mice, the researchers found that breast ducts were deformed and tumors typically developed after about one year's time. This dramatic result pointed to Scribble, a cell shape regulator, as a tumor suppressor in breast epithelial cells.

The targets of tumor suppressors are usually cancer-causing genes, or oncogenes, such as Myc, which past research has shown to be overexpressed,
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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