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Protein 'switch' suppresses skin cancer development
Date:9/8/2008

HOUSTON - The protein IKKalpha (IKKα) regulates the cell cycle of keratinocytes and plays a key role in keeping these specialized skin cells from becoming malignant, researchers at The University of Texas M. D. Anderson Cancer Center report in the Sept. 9 issue of Cancer Cell.

"We have shown that IKKα acts as a sentry, monitoring and, when necessary, halting proliferation of these important cells. In the first mouse model of its kind, we also found that deleting IKKα spontaneously induced squamous cell carcinomas by activating the epidermal growth factor receptor pathway," said senior author Yinling Hu, Ph.D., assistant professor in M. D. Anderson's Department of Carcinogenesis at the Science Park - Research Division in Smithville, Texas. "These results provide new therapeutic targets for prevention of skin cancer."

Keratinocytes originate in the basal layer of the epidermis to replace skin cells at the surface that have been shed. As keratinocytes gradually move up through the skin layers, they differentiate and eventually form the top layer of the skin, which is composed of squamous cells. The cycle ends through terminal differentiation, in which cells lose their ability to reproduce by dividing in two. They eventually die.

Hu and colleagues reported in research last year that a reduction in IKKα expression promotes the development of chemically induced papillomas and carcinomas, which are benign and malignant tumors of the epithelium respectively. Epithelial cells make up the outer layers of skin and the inner linings of many organs, including the lungs and the gastrointestinal, reproductive and urinary tracts. Most cancers originate in organ epithelial cells. The researchers also demonstrated that an intact IKKα gene is required to suppress skin cancer development.

Downregulation of IKKα has been noted in a variety of human squamous cell carcinomas, including those of the skin, esopha
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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