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September 26, 2006 • Volume 3 / Number 37 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Featured Article

Tanning Study Suggests Strategies for Preventing Skin Cancer

Researchers have identified a drug that bypasses a genetic predisposition and induces tanning in mice prone to sunburns and skin cancer. The result is "sunless" tanning that offers mice some protection against skin damage from ultraviolet (UV) light.

The drug, called forskolin, supplies a signal that's weak or missing in the skin cells of fair-skinned mice. Without this signal, the cells make red or blond pigment rather than brown or black.

By rubbing forskolin cream on fair-skinned mice once a day for several weeks, researchers at the Dana-Farber Cancer Institute caused the mice to produce dark pigment that was largely indistinguishable from that of brown or black mice.

The forskolin-induced tans offered protection against UV rays, even among mice predisposed to develop skin cancer, the researchers reported in the September 21 Nature.

"Many mice still got tumors, but darkening their skin significantly delayed the tumors and reduced their number," says Dr. David Fisher, who directs Dana-Farber's Melanoma Program and led the study.

The work was done completely in mice, Dr. Fisher adds, and more research is needed to understand the tanning "pathway" in humans and to assess potential treatments.

"The importance of this study is to show that you may be able to bypass genetic deficiencies in tanning that exist in people through topical agents," says Dr. Glenn Merlino, chief of Laboratory of Cell Regulation and Carcinogenesis in NCI's Center for Cancer Research (CCR), and a melanoma researcher.

"This study provides proof of principle that this concept could work, and its application to humans will depend on safety and other factors," adds Dr. Merlino.

Dr. Fisher's team began by characterizing the tanning pathway in mice. They reasoned that the pathways are similar in light- and dark-skinned mice except for a single protein, the melanocortin 1 receptor.

When dark-skinned mice are exposed to UV light, the melanocortin 1 receptors produce a strong signal that activates the chemical cAMP. This is essential for producing dark pigment.

But under the same conditions, the melanocortin 1 receptors of fair-skinned mice do not generate a strong signal. To bypass this "block" in the tanning pathway, the researchers gave the mice forskolin, one of several drugs that activates cAMP.

Forskolin effectively introduced a tanning response in mice that had never had one.

The melanocortin 1 receptor functions differently in light-skinned mice compared with other mice because of an alteration in the melanocortin 1 receptor (mc1r) gene.

Many fair-skinned people, particularly redheads, have inherited this variant gene, and the gene is associated with an increased risk of UV-induced skin cancers.

For people who live in Nordic regions with limited sunlight, a tanning response may block out UV rays that are needed to help process Vitamin D, leading to a deficiency or even death, notes Dr. Fisher.

But in sunny climates, tanning evolved as a response to UV light. "Tanning prepares the body for more UV exposure and protects against damage," says first author Dr. John D'Orazio, who is now at the University of Kentucky.

Forskolin protected mice against a form of squamous cell carcinoma, the most common skin cancer in humans. The researchers will investigate whether it protects against melanoma, an aggressive and often deadly skin cancer that is increasing in incidence worldwide.

"I think this research is a great example of how mouse models can be successfully used to gain novel insights into human disease and its prevention," says Dr. Merlino.

By Edward R. Winstead