An enzyme found at elevated levels in several human cancers has been linked to abnormal tumor growth in fruit flies, a discovery that provides a new model for understanding the link between stem cell biology and cancer, according to researchers at the University of Oregon.
Using fluorescent staining and laser-scanning microscopy, the eight-member research team studied various mutations in a gene called aurora-A to observe how changes in protein expression affected the ability of Drosophila neuroblasts, a type of neural stem cell, to maintain their stem cell character without forming tumors.
Reporting in the Dec. 20 issue of the journal Genes & Development, Chris Doe and colleagues detail how an overproduction of renewed neuroblasts in the flies can be traced to misregulation by the aurora-A kinase. This enzyme under normal conditions appears to be critical as a traffic cop for various proteins during mitosis in neuroblasts, they concluded.
"In humans, there has been a lot of thought that maybe stem cell populations are at the heart of many cancers," said Ryan O. Andersen, a doctoral student in Doe's lab. "The numbers are off drastically. Instead of properly dividing, they are overproducing more stem cells rather than maintaining a steady population. This loss of regulation leads to tumors populated with these overproduced cells."
Andersen and Cheng-Yu Lee, a postdoctoral fellow, were lead authors on the paper. Doe, a Howard Hughes Medical Institute investigator, is a professor of biology in the UO Institute of Neuroscience and Institute of Molecular Biology.
In Drosophila, Doe's team found that a mutation in aurora-A, an evolutionary conserved gene in fruit flies and humans, results in two distinguishing problems: Proteins (Numb) involved in the differentiation into neurons and neuroblast self-renewal (aPKC) are not sorted to their proper sides of the cell, and the mitotic spindle that provides cortical pol
Contact: Jim Barlow
University of Oregon