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Research study maps formation process of certain type of breast cancer

A slow-motion movie of the changes inside a breast cell as it becomes a particularly stubborn type of cancer cell would show a process very much like that depicted for the first time in a new study by researchers at Dana-Farber.

The investigators, led by Debajit Biswas, D.Sc., in the laboratory of Arthur Pardee, Ph.D., of Dana-Farber's Cancer Biology department, have charted the chain of events by which breast cancer cells known as estrogen receptor-negative (or ER-negative) cells are formed. Because such cells do not need the female hormone estrogen to grow and proliferate, conventional drugs like tamoxifen that block estrogen from acting on breast cells are generally ineffective against ER-negative tumors. About 30 percent of all breast cancers are ER-negative.

"The discovery of the steps involved in the creation of ER-negative breast cancer cells means scientists now have an array of targets for drugs that may be able to stop the process in its tracks, providing the first specific therapy for patients with ER-negative breast tumors," Biswas says.

Thus far, the studies have been conducted in laboratory samples of cells only.

The study, published in the most recent issue (July 18) of the Proceedings of the National Academy of Sciences, focuses on what happens after ER-negative cells have been stimulated to grow.

The on-off switch for growth in ER-negative cells is a "receptor" on the cell surface. When the receptor meets a substance called epidermal growth factor (EGF), it signals the cell to begin dividing uncontrollably.

In the new laboratory study, Biswas and his colleagues map out some of the key stages in the process of ER-negative cells' becoming cancerous (see Figure 1). One involves a protein complex called nuclear factor kappa B (NF-kB), which is activated when EGF docks at the cell. In its active form, NF-kB serves as an "ignition switch" for cell division.

The activation of NF-kB by EGF is itself a complex proc
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Contact: Todd Ringler
todd_ringler@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
23-Jul-2000


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