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St. Jude investigators discover role of several key genes in retina development; take large step toward preventing and curing deadly eye cancer retinoblastoma
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. The results of the study appear in the open-access journal BMC Biology.
The St. Jude investigators discovered that in mice the p107 gene is active before birth in the cells that are fated to produce the mature 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 actively multiplying retinal cells.
The study showed that if gene mutations knock out both p107 and Rb, the mice are at high risk of developing retinoblastoma. But if only p107 is knocked out, Rb can make up for that loss and prevent retinoblastoma; and if Rb is knocked out, p107 becomes more active to make up for that loss.
In the human retina, however, p107 is almost completely inactive, leaving RB1 to do most of the work. RB1 is the human equivalent of Rb in mice. Therefore, if RB1 suffers a mutation and becomes inactive, there is no backup gene in the human retina as there is in the mouse. The result: retinoblastoma.
“If we could figure out how to turn on the human p107 gene, it might be able to protect against retinoblastoma when RB1 is mutated,” said Stacy Donovan, PhD, a postdoctoral fellow in the Department of Developmental Neurobiology at St. Jude.
“Studying mouse models of retinoblastoma might also let us discover which of the various types of cells in the retina becomes cancerous and causes retinoblastoma,” added Brett Schweers, PhD, a postdoctoral fellow in the Department of Developmental Neurobiology at St. Jude. “Knowing which cell causes retinoblastoma would give researchers a specific target for a novel retinoblastoma drug.”
Donovan and Schweers are the first and second authors respectively of the paper and contributed equally to the work. Michael Dyer, PhD, an associate member of the Department of Developmental Neurobiology at St. Jude is senior author of the paper.
This work was supported in part by the National Institutes of Health, Cancer Center Support from the National Cancer Institute, the American Cancer Society, ALSAC, the Pearle Vision Foundation and Research to Prevent Blindness.
Last update: June 2006