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Genetic insights may explain retinal growth, eye cancer

Investigators at St. Jude Children's Research Hospital have discovered the role of several key genes in the development of the retina, and in the process have taken a significant step toward understanding how to prevent or cure the potentially deadly eye cancer retinoblastoma. Retinoblastoma is the third most common cancer in infants after leukemia and neuroblastoma (nerve cancer). Retinoblastoma that has spread outside the eye is among the deadliest childhood cancers, with an average survival rate of less than 10 percent.

A key finding of the new study is that humans are more susceptible to developing retinoblastoma than mice, because mice can compensate for the loss of a gene critical to normal retinal development while humans cannot. The results of the study appear in the open-access journal BMC Biology.

"Our study gives us important new information on the normal development of the retina and suggests new studies that could lead to the design of more effective drugs to treat retinoblastoma," said Michael Dyer, Ph.D., an associate member of the Department of Developmental Neurobiology at St. Jude and senior author of the paper.

The researchers discovered that during the development of the retina in mice, three genes that belong to the Rb gene family are expressed at different times. Specifically, the p107 gene is active before birth in cells that are going to become the retina. This gene ensures that the retinal cells stop multiplying at the proper time during development of this tissue. The Rb gene is expressed after birth in those cells that are actively multiplying as they also help form the retina.

In addition, the St. Jude team found that when Rb was inactivated during development of the mouse retina, the two p107 gene copies were up-regulated--made more active--therefore compensating for this loss of Rb activity. Importantly, this compensation required the presence of both p107 genes. In turn, when p107 was inactivated, Rb activity was
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Contact: Bonnie Kourvelas
media@stjude.org
901-495-3306
St. Jude Children's Research Hospital
8-May-2006


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