Spotlight on Research for 1999

December 1999 (historical)

Of Mice and Skin

Basal cell carcinoma (BCC), the most common of all human cancers, affects 750,000 Americans a year. In fact, estimates are that one in three Caucasians born in the U.S. after 1994 will develop such a skin cancer in their lifetime. Despite these sobering statistics, however, the battle against this and other tumor-producing skin cancers like squamous cell carcinoma (SCC) has just taken a turn for the better. With support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), scientists have notched two recent victories: the first mouse model of human BCC and a reduction in mouse SCC tumors by the COX-2 inhibitor celecoxib.

At least one mouse model of skin cancer--that of SCC--has been created experimentally by exposure to ultraviolet (UV) light. This model has yielded much information about the genetic and cellular components of the disease. But until recently, scientists had been unable to produce BCC-like tumors in mice either through chemicals, UV light exposure, or ionizing radiation. Now, the University of California, San Francisco's Michelle Aszterbaum, M.D., and her colleagues have found that ptch+/- mice, which have an alteration in the tumor suppressor gene, develop a high incidence of BCC-like tumors in response to chronic UV exposure or a single dose of ionizing radiation. This discovery confirms the importance of protecting against UV and radiation in preventing human skin cancer. And because this new mouse model can reproduce tumors that have similarities to BCC tumors, it is ideal for testing gene therapy, chemoprevention, and chemotherapy against human tumors.

At the University of Rochester Medical Center in New York, Alice Pentland, M.D., and her colleagues have used another laboratory mouse--the hairless mouse--to move toward improved treatment for SCC. In their study, mice with SCC tumors produced by previous UV light exposure were divided into two groups: a control group and one fed a diet containing celecoxib, a new COX-2 inhibitor used in the treatment of arthritis. (COX-2 inhibitors block an enzyme known to stimulate inflammation in the body.) After 10 weeks, the mice fed the celecoxib diet had about half the number of tumors present in the control group. The drug was most effective at reducing new SCC tumor formation, suggesting that celecoxib might be a useful way to prevent some human skin cancers resulting from previous UV light exposure. However, additional studies need to be done.

"These two studies will definitely help us bring skin tumors into sharper focus," said NIAMS Director Stephen I. Katz, M.D., Ph.D., a dermatologist who also heads the National Cancer Institute's Dermatology Branch. "We're seeing the best of basic and translational research at work."

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Aszterbaum M, Epstein J, Oro A, Douglas V, LeBoit P, Scott M, Epstein E Jr. Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice. Nature Medicine 1999;5(11):1-7.

Pentland A, Schoggins J, Scott G, Khan K, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999;20:(10):1939-44

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), leads the Federal medical research effort in arthritis and musculoskeletal and skin diseases. The NIAMS supports research and research training throughout the United States, as well as on the NIH campus in Bethesda, MD, and disseminates health and research information. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at http://www.niams.nih.gov/.