St. Jude Finds Signaling System That Halts the Growth of a Childhood Br...( Researchers discover that protein...),Health

Researchers discover that proteins BMP2, BMP4 and BMP7 inhibit the growth of medulloblastoma tumors, while inducing malignant cells to develop into normal neurons, a finding that may lead to better treatments for the cancer

MEMPHIS, Tenn., March 14 /PRNewswire-USNewswire/ -- A discovery by St. Jude Children's Research Hospital scientists suggests a safer way to treat medulloblastoma, a rare but often fatal childhood brain tumor. The group found that one of the brain's signaling pathways inhibits the growth of the highly aggressive cancer cells.

The researchers discovered that three proteins, designated BMP2, BMP4 and BMP7, halted the growth of medulloblastoma tumors and induced the malignant cells to develop into normal neurons.

"We think we have identified a pathway that can be used to prevent tumor formation and a potential target for therapy," said Martine F. Roussel, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology. A report on this work appears in the March 15 issue of "Genes & Development." Roussel is the paper's senior author. Several research teams are seeking to decipher the intricate signaling mechanisms that govern the proliferation of cells called granule neuron progenitors (GNPs). These cells go on to develop into neurons in the cerebellum during the first year of life. But the disruption of this differentiation process can trigger medulloblastoma.

Previous research had shown that spurring GNPs to differentiate into neurons requires that BMPs bind to a set of receptors on the cell surface. This binding results in blocking the activity of a signaling pathway triggered by another molecule called Sonic hedgehog.

"What was not known, and what we now find, is that the effect of BMPs on normal GNP cells is almost exactly mimicked in GNP-like tumor cells," Roussel said.

In cell culture experiments, her group found that BMPs rapidly cause the degradation of a protein calle
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