Telomere crisis is crucial stage in development of breast cancer.

2004 SEP 2 - (NewsRx.com & NewsRx.net) -- 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 U.S. Department of Energy's Lawrence Berkeley National Laboratory and the University of California at San Francisco (UCSF).

Their report was published August 9, 2004, in the advance online version of Nature Genetics.

In the breast, cells in a milk-collecting duct occasionally proliferate excessively as a result of development of a regulatory defect. Joe Gray, director of Berkeley Lab's Life Sciences Division and a professor of laboratory medicine and radiation oncology at UCSF, 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 carcinoma in situ." Should the cancer progress further, it next invades other parts of the breast and may escape to other organs.

Not all cancer researchers agree that telomere crisis in hyperplasia, followed by reactivation of telomerase, leads to carcinoma in situ - and thence, sometimes, to invasive cancer; they assign cancer to other causes. In part the disagreement arises because sequential events can't be followed in individual tissue samples from living subjects.