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Mutations in different cells cooperate to set the stage for cancer
Date:1/13/2010

RasV12 exists in one group of cells, and scrib- exists in a nearby group of cells. They decided to find out, using the fruit fly Drosophila melanogaster, a model organism that has been a workhorse of geneticists over the years. To its surprise, Xu's group discovered that the two mutations, existing in adjacent clusters of Drosophila larval eye cells, somehow interacted to turn the entire group of cells into a large invasive tumor. The results were dramatic, Xu says. It was just as if the two mutations had existed in a single cell.

"No one has ever shown before that different oncogenic mutations in different cells can interact to produce a tumor," said Xu. "People have just assumed that when they take the DNA from a tumor, the various mutations they see are combined in each cell. But they could be in different cells. Nobody really knows."

The team observed a similar result when they grew cells with the RasV12 mutation together with cells that harbored a dysfunctional mutant of another tumor-suppressor gene, lgl. That led them to wonder whether the old paradigm of oncogenesis - that cancer-causing mutations must exist in the same cell -- might be in need of revision.

Since their results indicated that the genetic "cooperation" long thought to be necessary for tumor formation could actually occur between cells, Xu's team wanted to find out how this could happen. By sifting through some of the genes activated in the RasV12 plus scrib- combination, they found the signaling pathway that mediates the interaction. They showed that cells that contain the scrib- mutation activate a signal protein called JNK, which in turn drives a signaling pathway that promotes cellular proliferation. When this JNK-driven activity reaches cells that contain RasV12, the combination of these two cell-proliferating influences appears to be enough to push the cells in
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
Source:Eurekalert

Page: 1 2 3

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