Mutant B-Raf Protein Reduces Melanoma Development

Lowering protein B-Raf reduces
melanoma development
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"Our studies suggest that using therapies to target and inhibit the function of mutant V599EB-Raf protein could prevent the spread of melanoma for those melanomas containing the B-Raf mutation," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology, and dermatology, Penn State College of Medicine.

The job of normal non-mutated B-Raf is to relay signals from the cell membrane, which is the boundary of the cell receiving the signals, to the nucleus, which contains genetic material and controls many of the cell's activities. B-Raf is one member of the chain that relays signals playing an important role in cell signalling. The protein is usually only active when needed to relay signals.

In contrast, mutant B-Raf is active all the time, which disrupts the chain's normal function. Previous studies have shown B-Raf is the most mutated gene in melanomas, present in about 60 percent of human melanomas, but the role mutant B-Raf plays in causing melanoma tumours remained unknown.

Robertson used human melanoma cells, applying siRNA, small interfering ribonucleic acids, or BAY 43-9006, a general Raf inhibitor. "Reducing B-Raf activity in melanoma cells before tumours had formed significantly decreased the growth potential of the melanoma cells and, in effect, prevented tumour development," Robertson said. "In contrast, reducing B-Raf activity in existing tumours in a mouse model did not shrink the tumours but did prevent them from getting bigger.

The study shows that in existing melanoma tumours, inhibiting V599EB-Raf activity reduced vascular development, which is essential for tumour growth. Without vascular support the tumours remained the same size.; Source: Penn State College of Medicine