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

icate when mammary epithelial cells have escaped senescence, and how far they had progressed toward genomic instability. These markers, they say, could ultimately be used to evaluate the susceptibility of epithelial cells to becoming cancerous and thus point to cells that could be potential targets for prevention and therapy at a precancerous or early cancerous stage.

Cells begin the slide toward the cancerous state when they start to accumulate mutations in the genes involved in regulating a cell's growth. Once enough critical genes have been affected, a cell progressively loses its cell-cycle control, becomes singularly focused on proliferating and eventually breaks out of its tissue membrane. (See image: http://pubaffr.ucsf.edu/imagedb/imsearch.php3?iname=0130200118)

The genesis for the researchers' investigation was, in part, to seek an explanation for why the majority of cancers originate in epithelial cells. They did so by examining and comparing the molecular pathways leading to cancer development in normal fibroblasts -- which make up the connective tissue of the body, including in the breast -- and epithelial cells. Epithelial cells line the outside of the body, the passage ways leading to and from the body's surface, and the portion of the ducts and glands that secrete fluids - including the glands and ductal structures of the breast that develop breast cancer.

While fibroblasts account for some cancers, epithelial cells are the basis of cancers of the breast, prostate, colon and skin, among others.

The researchers placed the two cell types, both derived from normal breast tissue, in separate culture dishes to observe their growth patterns. The differences were quickly apparent.

The fibroblasts displayed the classic characteristics of normal cell behavior. They maintained an active cell cycle for several weeks -- growing, duplicat
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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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