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Researchers from Harvard Medical School in the U.S. found that redheads are more likely to develop a severe form of skin cancer.
The study demonstrates that the same mutation responsible for the red color of the hair also promotes an important pathway causing the disease.
The research reveals that the discovery of gene alteration melanocortin-1 receptor (MC1R) helps to explain the molecular mechanisms underlying the risk for developing melanoma redheads, providing new perspectives for the treatment and prevention of this dangerous type of skin cancer.
"In this study, we demonstrate that mutation-MC1R RHC promotes PI3K/Akt signaling pathway, when a guy with red hair is exposed to UV radiation," explains senior study co-author Wenyi Wei.
PI3K/Akt pathway is known to cause cancer which has been implicated in breast cancer, ovarian cancer and lung cancer.
Previous work demonstrated that MC1R plays a key role in protecting melanocytes of DNA damage induced by UV. In the present study, the team wanted to understand how this happened.
The team embarked on a series of experiments both in cell cultures and in mouse models. The experiments showed that, under normal circumstances, MC1R binds to PTEN tumor suppressor gene. PTEN acts to protect against cancer without PTEN, however, the end result is greater P13K/Akt signaling pathway in causing cancer.
The team then went on to demonstrate that mutations in MC1R RHC-found in people with red hair did not have this protection mechanism. "As a result, after UV exposure, we saw an increase in the destruction of pigment cells in PTEN mutant," says Wei.
The team also found that, in these same cells with pigment-MC1R RHC, the high activity of PI3K/Akt increased cell proliferation and was synchronized with other cancer-causing mutation in the BRAF gene.
According to the researchers, the expression of the mutation in the gene BRAF in melanocytes of mice carrying the mutation in MC1R led to a high incidence of invasive melanomas.
"Our results provide a possible molecular mechanism that explains why people with red hair who harbor mutations in MC1R are much more susceptible to skin damage induced by UV than those with darker skin, the researchers conclude.
The staff believed that these new data suggest that inhibitors of drugs targeting the PI3K/Akt signaling pathway could be used in combination with Vemurafenib, a drug that targets the BRAF oncogenic protein to treat melanoma patients who have both variants BRAF as MC1R.