In a developing animal, stem cells proliferate and differentiate to form the organs needed for life. A new study shows how a crucial step in this process happens and how a reversal of that step contributes to cancer.
The study, led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, shows for the first time that three proteins, called E2f1, E2f2 and E2f3, play a key role in the transition stem cells make to their final, differentiated, state.
These proteins help stimulate stem cells to grow and proliferate. But once stem cells begin to differentiate into their final cell type - a cell in the retina or in the lining of the intestine, for example - the same three proteins switch function and stop them from dividing any more.
The research also shows how these proteins can switch course yet again in cells that have mutations in the retinoblastoma (Rb) gene. Mutated Rb genes occur in many types of cancer, suggesting that these E2f proteins might offer a safe and novel therapeutic target in these tumors.
The findings are published in back-to-back papers in the Dec. 17 issue of the journal Nature.
"We show that these E2fs are gene activators in stem cells but then switch to gene repressors when stem cells begin differentiating," says Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at Ohio State's James Cancer Hospital and Solove Research Institute. Leone headed the first of the two Nature studies and is a co-author on the second.