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New model of skin cancer provides insights on second-most common type of cancer
Date:12/10/2009

PHILADELPHIA Scientists at the University of Pennsylvania School of Medicine have developed a new model of skin cancer based on the knowledge that a common cancer-related molecule called Src kinase is activated in human skin-cancer samples.

"Our previous work demonstrated that Src kinases are activated in human squamous cell carcinomas of the skin. We modeled these observations by increasing the expression of the gene Fyn, a member of Src family of proteins, in mouse skin," explains senior author John T. Seykora M.D., Ph.D, assistant professor of Dermatology. In addition, prior work by the Seykora lab on a related protein called Srcasm, discovered by him in 2002, suggested that Srcasm may function as an anti-oncogene, a molecule that keeps others in check in order to control cell growth.

In this proof-of-principle study, published this month in Cancer Research, the authors found that genetically engineered mice expressing a K14-Fyn transgene develop precancerous lesions and invasive squamous cell carcinomas (SCCs) spontaneously in 5 to 8 weeks. Skin SCCs are the second most common form of cancer, with greater than 250,000 cases annually in the US, leading to approximately 2,500 deaths.

This study demonstrates that Fyn is a potent oncogene in skin. When Srcasm levels are raised in the mouse skin cancer model, tumor formation is dramatically inhibited showing that Srcasm functions as an anti-oncogene.

The findings highlight an important relationship between Fyn and SrcasmFyn encourages growth, while Srcasm inhibits it. "When this system malfunctions, it's like stepping on the gas and taking off the brakes on cell growth," explains Seykora. "Adding Srcasm back to the system lowers Fyn levels and restores order."

Analysis of human skin tumor samples confirmed that Srcasm levels are decreased and Src kinase activity is increased. The authors conclude that one potential means of combating skin cancer
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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