Gene that prevents cancer also controls the skin's suntanning machinery

A gene that prevents cancer also controls the skin's suntanning machinery, researchers report in the March 9, 2007 issue of the journal Cell.

"The p53 tumor suppressor is commonly mutated in human cancer," explained David Fisher, director of the Melanoma Program in Medical Oncology at Dana-Farber Cancer Institute. "Now, we've found that it plays a role in the skin's tanning response."

The researchers also linked the p53-driven process to other instances of skin darkening not associated with the sun.

It is the most superficial cells in skin that react to sun exposure, Fisher said. When those "keratinocytes" are exposed to the sun, they produce melanocyte-stimulating hormone (MSH), triggering other cells to manufacture the skin-bronzing pigment.

Variation in tanning ability stems from differences in the MSH receptor, Fisher said. For example, the receptor variant found in redheads doesn't respond to MSH, leaving them unable to tan.

However, researchers hadn't identified the factors ultimately responsible for the tanning hormone's production.

MSH is one product of a larger gene sequence that also encodes the natural morphine-like substance, called beta-endorphin, Fisher added. While MSH drives the suntan response, beta-endorphin is believed to drive sun-seeking behavior.

Fisher's team showed that mice require p53 in order to switch on genes that produce MSH and tan. Similarly, the induction of beta-endorphin by the sun also depends on p53.

"The induction of beta-endorphin appears to be hard-wired to the tanning pathway," Fisher said. "This might explain addictive behaviors associated with sun-seeking or the use of tanning salons."

The researchers observed similar events in human skin to those seen in the mice. They also found evidence implicating p53 in other forms of abnormal skin pigmentation that can result as a side effect of certain drugs or other stresses.

"Certain drugs are probably inadvertently activating p53 and, with it, the sun-tanning pathway," Fisher speculated. "We might now be able to find ways to interfere with this process to prevent it from occurring."

By the same token, a more complete understanding of the suntan process could lead to products that can produce a tan safely without exposure to potentially damaging UV radiation-even in those people who otherwise don't tan. Fisher said he is involved in a small biotechnology company that is working to develop such a product.

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