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The telomere crisis: A crucial stage in breast cancer

BERKELEY, CA -- Telomere crisis is an important early event in the development of breast cancer, and its occurrence can be identified with precision, according to recent findings by a team of scientists at the Department of Energy's Lawrence Berkeley National Laboratory and the University of California at San Francisco. Their report is now available through advance online publication of Nature Genetics.

Joe Gray, director of Berkeley Lab's Life Sciences Division and a professor of laboratory medicine and radiation oncology at UCSF, is one of the paper's lead authors, with Koei Chin and Britt Marie Ljung of UCSF; Carlos Ortiz de Solorzano, Paul Yaswen, and Martha Stampfer of Berkeley Lab; and Stephen J. Lockett from the National Cancer Institute.

In the breast, cells in a milk-collecting duct occasionally proliferate excessively due to development of a regulatory defect. Gray and his colleagues postulate that this results in a lesion called "usual ductal hyperplasia."

"The chromosomes in these growing cells lose a hundred or so base pairs of DNA every time they divide," Gray explains, "because the usual DNA replication processes don't copy DNA all the way out to the ends of the chromosomes. This erodes the DNA sequences that interact with proteins to form structures called telomeres, which protect the chromosome ends."

Eventually the DNA ends erode so much they can no longer protect the chromosomes. When this happens the chromosomes become unstable, and damage-control mechanisms kick in that kill the unstable cells. This process, known as "telomere crisis," normally protects against inappropriate long-term cell growths like cancer.

Gray and his colleagues believe that "very rarely, the chromosome instability activates a specialized DNA-replication complex, telomerase, which can restore telomeres. Cells in which telomerase is activated can then proliferate indefinitely to form the next stage of cancer, known as 'ductal car
'"/>

Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
10-Aug-2004


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