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CSHL study unmasks a stem cell origin of skin cancer and the genetic roots of malignancy
Date:2/3/2011

Cold Spring Harbor, N.Y. A constellation of different stem cell populations within our skin help it to cope with normal wear and tear. By constantly proliferating, the stem cells allow skin to replenish itself, allowing each cell to be replaced by a new one about once a month. But the normal cycle of division and death within one or more of these stem cell types can sometimes be derailed by genetic mishaps. Such events are believed to spawn carcinomas and other deadly skin cancers, which are the mostly frequently diagnosed cancers in the United States.

Researchers at Cold Spring Harbor Laboratory (CSHL) led by Associate Professor Alea A. Mills, Ph.D., have now unmasked a long sought stem cell origin of carcinoma and identified the genetic lesions occurring within these cells that spur them on to malignancy. Her team has found that increased activity of a powerful oncogene called Ras combined with overly exuberant activity of a protein called ΔNp63α, stimulates the population of skin stem cells that produce keratin 15one of many keratin proteins found in the skinpromoting carcinoma development. These findings appear online on February 4 in the journal Cell Stem Cell.

When cells in the skin or anywhere else in the body sense a potentially cancer-causing threat such as an activated oncogene like Raswhich speeds up cell divisionthe cells cope by slamming on the brakes to trigger a process called senescence. This is a tumor-suppressive mechanism that halts cell division while allowing cells to stay metabolically active.

"Unfortunately there are a number of genetic events that can bypass senescence and push a cell down the road towards cancer," says Mills. The loss of a gene called p53, a powerful tumor suppressor, in senescent cells is one such event.

Mills's group has long focused on p53's sister gene p63, which she discovered during her postdoctoral years. As Mills found subsequently, adult mice that lack p6
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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