January 14, 2003
Study aims to solve puzzle of ER-negative breast tumors
A model of breast cells
Investigating the problem calls for great ingenuity. At Harvard Medical School, cell biologist Joan Brugge, PhD, has developed a way to create hollow balls of breast cells, or "acini," in the laboratory, that mimic the basic unit of milk duct tissue in the breast where most cancers form. She inserts growth factor molecules into the cell clusters so she can observe normal or cancerous development.
Under a microscope, brown stain identifies ER-positive breast cells.
ER-negative tumors, says Dr. Brugge, exhibit abnormally high levels of a variety of growth factor receptors, one or more of which might be involved in the cells' cancerous transformation. "What we're doing is using our model to determine which growth-factor receptor pairs cause changes similar to those that occur in human breast cancer," she explains.
The most gratifying outcome, says Dr. Brugge, would be to identify key regulators of cell growth that are damaged in the cancer cells. "Those would be really good targets" for new, specific designer drugs with few or mild side effects. Collaborating with Dr. Brugge on the growth-factor signaling project are Dr. Brown and Thomas Roberts, PhD, also of Dana-Farber.
In the light blue stain, these ER-negative cells lack estrogen receptors.
Discovering targets for prevention of ER-negative cancers is also a major goal. In another of the six projects, Dr. Brown, Judy Garber, MD, MPH, and Bruce Spiegelman, PhD, will research whether a protein known as PPAR-gamma might prevent or slow the development of tumors. Dr. Spiegelman says that in several types of cancer cell lines grown in the laboratory, the protein — originally discovered as a regulator of fat cells — has acted as a "tumor suppressor," halting the proliferation of cancer cells, including breast cancer cells. The scientists will use animal models of ER-negative breast cancer to determine whether activating PPAR-gamma might be a valid weapon against the disease. They'll also use "ductal lavage," a method of extracting fluid from the nipple, to monitor the effects of potentially cancer-preventing drugs in patients.
Next page: Hunting for overactive genes
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