A critical event in the development of melanoma and other human cancers is the inactivation of a gene known as "p16." Normally, p16 keeps cells from growing rapidly, a condition that sometimes leads to tumor formation. Working with mouse epidermis and cultured human melanoma and nonmelanoma cancer cells, the team found that p16 inactivates key enzymes -- called JNK 1 and JNK 2 -- in the process. The enzymes are normally activated by exposure to ultraviolet light. By shutting down the enzymes, p16 keeps them from activating a huge complex of proteins, which, when active, attaches to chromosomes and turns on many genes that promote cell growth.
The p16 gene works by producing a protein that attaches to the enzymes, preventing them from performing their function. When the researchers added the p16 protein to colonies of cancer cells in culture, it diminished the size of many colonies, wiping out some of them. It also decreased the total number of cancer cells.
The researchers have designed a very small protein that mimics the action of the natural p16 protein.
"We hope this [small protein] will have anti-cancer activity," said Dong. "We are testing it now." A patent application on the protein has been filed. Dong said he hopes to see clinical trials of this or similar treatments begin in a few years.
The work was funded by the National Institutes of Health and the Hormel Institute.
Nature Structural & Molecular Biology