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Fundamental finding yields insight into stem cells, cancer; opens door to drug discovery

DURHAM, N.C. New research by investigators at Duke University Medical Center has provided insight into a fundamental cellular control mechanism that governs tissue regeneration, stem cell renewal and cancer growth. In humans, malfunctions in the pathway have been implicated in skin and brain cancers, as well as certain developmental defects, according to the researchers.

The team found that the protein beta-arrestin2, earlier linked to a variety of inhibitory functions, also plays a critical role in activating the so-called hedgehog (Hh) signaling pathway, which plays a central role in early development and normal cell proliferation. When left unchecked, uncontrolled cell growth spurred by the hedgehog pathway can lead to the development of cancerous tumors.

The researchers report their findings in the Dec. 24, 2004, issue of Science. The work was funded by the National Institutes of Health.

"Studies have found a wide breadth of functions for beta-arrestins, but none had revealed a role for these proteins in development," said James B. Duke Professor Marc Caron, Ph.D., a researcher in the department of cell biology, the Duke Institute for Genome Sciences and Policy and senior author of the study. "The involvement of beta-arrestin2 in the hedgehog signaling pathway provides a previously unappreciated paradigm for its role in promoting growth, differentiation, and malignancies."

The finding in zebrafish could lead to new drugs that block the growth of tumors by disrupting the beta-arrestin2 protein's normal function, the researchers said. In other cases, drugs that activate beta-arrestin2 might also drive the proliferation of therapeutic stem cells, they added.

Hh proteins play a central role in cell proliferation and embryonic patterning. In humans, inhibitory mutations in the pathway result in developmental defects such as holoprosencephaly an often fatal condition characterized by abnormal brain development and facial defor
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
23-Dec-2004


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