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Ras gene causes cancer via different pathways in humans vs. mice

DURHAM, N.C. Researchers at the Duke Comprehensive Cancer Center have found that a known cancer-causing gene, Ras, may exert its influence through very different pathways in humans than in mice, a finding that could offer tantalizing new targets for anti-cancer therapy.

While studying the Ras gene, Duke researchers unexpectedly found that it activates an obscure group of proteins in humans, but not in mice, in order to turn normal cells malignant. Yet many cancer treatments are based on data scientists derive from mouse models.

"Our study highlights a little-known pathway that appears to play a critical role in the ability of Ras to transform human cells, but not mouse cells, to become tumorigenic," said Christopher Counter, Ph.D., a cancer biologist at the Duke Comprehensive Cancer Center. "This pathway could present a new protein target for anti-cancer drugs in humans, and it reinforces the inherent differences between human and mouse cancers in terms of how they evolve."

Results of the Duke study are being published in the Aug. 15, 2002, issue of Genes and Development.

The Duke researchers decided to study oncogenic Ras, one of the first genes found to be involved in human cancers, because it is associated with very different malignancies in humans than in mice. Ras is activated in one-third of all human cancers, and as high as 90 percent in specific cancers, like pancreatic. In mice, Ras is associated with breast, skin and lung cancers.

Despite these differences, it was assumed that Ras signals the same set of proteins in mice as it does in humans for cells to become cancerous. The Duke scientists challenged this assumption and studied, for the first time, how Ras transforms human cells.

Team members Nesrin Hamad, Ph.D., and Joel Elconin, M.D., set out to map how Ras communicates with various signaling pathways that, when over-activated, ultimately command cells to proliferate uncontrollably. The sci
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Contact: Rebecca Levine, Richard Puff
Levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
14-Aug-2002


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