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UCSF-led study points to pivotal, early event in cancer development

Researchers led by UCSF scientists report that they may have identified a pivotal - and very early -- event in the development of breast cancer, with an unexpected revelation regarding the behavior of mammary epithelial cells. The finding, they say, could point to a new target for very early detection and treatment of breast cancer.

The investigation was conducted in cell culture studies of mammary epithelial cells, in which breast cancer develops. However, because greater than 90 percent of cancers originate in epithelial cells, the finding could have broader implications for understanding carcinogenesis, says the senior author of the study, Thea Tlsty, PhD, UCSF professor of pathology.

The discovery was an outcome of studies supported by the UCSF Breast SPORE (Specialized Program in Organ Research Excellence), a funding mechanism established by the National Cancer Institute aimed at supporting basic scientists in work on translational research.

In their study, the researchers discovered that mammary epithelial cells are unexpectedly prone to spontaneously surmounting a built-in regulatory control on cell growth known as senescence, and that when they do escape this check, they almost always develop the multiple, simultaneous genetic changes associated with the earliest stages of cancer development.

"Until now, we've thought senescence could be relied upon as a barrier to continued cell growth," says Tlsty. "Our cell culture study of mammary epithelial cells suggests otherwise.

"We hypothesize that the mammary epithelial cells escape from senescence and acquire genomic instability to produce the types of genetic changes that occur at the very beginning of breast cancer. Our next step is to determine if these changes take place in animal models. Nobody has understood why the majority of cancer cells are epithelial in origin. This finding offers a possible explanation."

The researchers identified molecular markers that ind
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
30-Jan-2001


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