Researchers in Vienna have developed a mouse model they say can be used to identify which combinations of oncogenes lead to the development of cancer. The Multi-Hit mouse uses the Cre-recombinase system to generate random combinations of correctly and incorrectly orientated oncogenes, which are activated by effectively flipping them over.
The developers, led by researchers at the Laboratory of Robert Eferl, M.D., at the Ludwig Boltzmann Institute for Cancer Research, tested the system to evaluate the requirement for cooperating mutations in Ras-related cancers. Their results showed that Ras mutation alone wasn’t enough to cause tumor development, but when downstream effector genes MAPK, RALGEF, and PI3K were also activated, the animals did invariably develop tumors. Activation of PI3K alone was also sometimes enough to trigger tumor formation in the Ras mice, but only in very rare cases was just one of the other two genes capable of prompting cancer to develop.
“Our work on Ras has given important clues to possible therapeutic strategies," Dr. Eferl states. “More importantly, the results show that our Multi-Hit mouse can indeed be used to study interactions between gene mutations. This should make it much easier for us to understand how cancer arises and what we can do to treat it.”
The researchers describe their work in Nature Methods, in a paper titled “A mouse model to identify cooperating signaling pathways in cancer.”