Melanoma is one of the least common types of skin cancer, but it is also the most deadly. Melanocytes (pigment-producing skin cells) lose the genetic regulatory mechanisms that normally limit their number, allowing them to divide and proliferate out of control. One such regulator, called MITF, controls an array of genes that influence melanocyte development, function and survival. Researchers recently used a melanoma mouse model, cell cultures and human tissue samples to unravel the relationship between MITF and ATF2, a transcription factor (or protein that controls gene expression) that is more active in melanomas. The study, published December 23 in PLoS Genetics, demonstrates that the MITF is subject to negative regulation by ATF2, and such regulation is a key determinant in melanoma development. This work also reveals that the ratio of ATF2 to MITF in the nucleus of melanoma cells can predict survival in melanoma patients – relatively high amounts of ATF2 and correspondingly low MITF levels were associated with a poor prognosis.

“In the late 1990s, we began to observe that if you can inhibit ATF2, you can inhibit melanoma,” explained Dr. Ze’ev Ronai, senior author of the study and associate director of Sanford-Burnham’s National Cancer Institute-designated Cancer Center. “This latest study provides the first genetic evidence to support those initial observations. Here we show that mice lacking ATF2 in melanocytes do not develop melanoma even if they carry mutations seen in human melanoma. Moreover, ATF2 expression patterns can predict outcome in melanoma patients.”

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