HOUSTON, Jan. 18, 2007 -- Michael Stern's latest research into the formation of neurofibromatosis tumors reads something like a federal racketeering indictment, except that Stern's tracing proteins instead of laundered money, and he's looking not at offshore accounts but at biochemical paths of cause and effect.
The research, which appears in the Jan. 10 issue of the Journal of Neuroscience, seeks to find the biochemical pathway that's responsible for tumors in people with the genetic disorder neurofibromatosis. Stern built his case much like a prosecutor, compiling evidence from dozens of painstaking experiments on mutant fruit flies, each with a specific genetic flaw that testified to the power of one or more proteins involved.
Neurofibromatosis is characterized by the formation of tumors of peripheral nerve cells. Scientists know the disease is caused by defects in a gene called Nf1, but they have yet to find out precisely how the defective genes cause tumors to form.
"Our results suggest that having a defect in Nf1 begins a kind of biochemical domino effect that eventually leads to tumor growth," said Stern, professor of biochemistry and cell biology.
Stern's research group used fruit flies for several reasons: the insect's genome has been sequenced; it takes only two weeks to grow an new generation of fruit flies; and scientists know which fruit fly genes are analogous to the human genes associated with neurofibromatosis.
In preparing for its experiments, Stern's group knew that Nf1 encodes a protein called neurofibromin that inhibits the effect of a second protein called Ras, which is known to promote nerve cell growth. They also knew that a third protein called PI3K was recently reported to be hyperactivated in mice that had defective Nf1 genes, and they knew that PI3K requires the activity of a fourth protein called Akt, to carry out its tasks.