Proteins That Play Major Role in Melanoma Development Identified

Two proteins have been found to play a major role in the development of a mole into a deadly melanoma by Penn State scientists.

The researchers have also demonstrated that therapeutic targeting of these proteins is necessary for drugs to effectively treat this deadly form of cancer.

"We have shown that when two proteins - (V600E)B-Raf and Akt3 - communicate with one another in a mole, they cooperate leading to the development of melanoma," said Gavin Robertson, lead author and associate professor of pharmacology, pathology and dermatology, and director of the Foreman Foundation Melanoma Therapeutics Program at the Penn State College of Medicine Cancer Institute.

"We have also shown that effective therapies for melanoma need to target both these proteins, which essentially eliminates the tumors," he added.

Melanoma is the most deadly form of skin cancer because it metastasizes or moves around the body so quickly.

In recent years, researchers have zeroed in on two key genes - B-Raf and Akt3 - that cause this deadly cancer, and which could be important targets in the treatment of melanoma.

B-Raf is the most mutated gene in melanoma. The mutant protein, (V600E)B-Raf, produced by this gene is important in helping mole cells survive and grow but it is unable to form melanomas on its own.

In the latest study, the research team has found that a second protein - produced by Akt3 - regulates the activity of the mutated B-Raf, which aids the development of melanoma.

"What we have found is a second event that is necessary for melanomas to develop," added Robertson.

While comparing proteins within normal moles and human melanoma cells, the Penn State researchers noticed that the two proteins were communicating with one another only among melanoma cells but not among normal cells.

When the Akt3 protein was put into cells in conjunction with the mutant B-Raf gene, they were better able to form melanomas compared to cells just containing the mutant B-Raf gene.

"This tells us that you can have a mole but it cannot turn into melanoma without the presence of the Akt3 protein," explained Robertson.

While it is still unclear what brings the B-Raf and Akt3 proteins together, the Penn State researchers say they now have a better understanding of how these two proteins interact to cause melanoma.

The initial mutation of the B-Raf gene helps to create moles, but high levels of B-Raf activity due to the mutation prevents the cells from becoming a melanoma. It is only when the Akt3 protein is present in those cells and communicates with B-Raf that it lower its activity, thereby creating favorable conditions within the mole for cells to multiply, and allow them to turn into a melanoma.

Robertson said the discovery could pave the way for newer and more effective treatments for melanoma.

The study is published in the journal Cancer Research.

Source-ANI
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