DiGiovanni's research team has recently shown that STAT3 is involved in the development of skin cancer and began investigating its role in psoriasis, another disease in which skin cells grow inappropriately.

STAT3 belong to a class of proteins called transcription factors, potent proteins that can set off a cascade of events by simultaneously activating many genes. In the case of STAT3, activation leads to the production of growth-promoting and cell survival proteins. Activated STAT3 is essential in normal skin to promote wound healing. When the healing process is complete, normal STAT3 returns to its inactive form. But when it fails to turn off, the wound healing process continues and skin cells proliferate.

The researchers first looked for activated STAT3 in the skin of psoriasis patients and found high levels of activated STAT3 in psoriasis lesions in 19 of 21 patients. Based on this observation, the researchers decided to develop a mouse model in which the gene that encodes STAT3 is always turned on in the keratinocyte skin cells. When the genetically altered mice were born they looked relatively normal, but by the time they were two weeks old, they began to develop scaly patches on their tails that sometimes spread to their lower back. When the scientists examined skin samples from the scaly patches they discovered that the patches mimicked human psoriasis very closely.

"This mouse model recapitulated all of the major epidermal and immunological features of human psoriasis, something that other animal models fail to do," said DiGiovanni.

The researchers also noticed that if the animals suffered an abrasion, such as when they scratch themselves, they frequently developed a scaly lesion in the irritated area, just as many people develop psoriasis lesions after a mild injury - a characteristic called the Koebner phenome
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Contact: Julie A. Penne
jpenne@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
12-Dec-2004