Retinoblastoma Teacher of Cancer Biology and Medicine 英文参考文献.docVIP

Open access, freely available online Perspectives Retinoblastoma:Teacher of Cancer Biology and Medicine Alfred Knudson D espite its low incidence, retinoblastoma has attracted the great interest of not just their already known transforming factors. Showing this inactivation was, historically, critically important in resolving con?icting notions of viral versus genetic oncogenesis, just as the RNA tumor viruses directed investigators to proto-oncogenes. formation of the precursor and its malignant transformation. Making Further Clinical Progress pediatric oncologists, but also cancer biologists and oncologists who treat cancer in adults. Retinoblastoma reminds us that rare conditions with a hereditary component may be rare for a reason—the genes associated with them are important biologically. It is hardly surprising then that retinoblastoma continues to be a subject of interest to a large group of clinicians and scientists, as described by Dyer and colleagues in this issue of PLoS Medicine [1]. Further clinical progress may depend on a deeper understanding of the mechanisms of transformation in cells with defective or absent RB protein. Still unanswered is the following Lessons for Other Cancers Pediatric oncologists treating question: why is RB1 a retinoblastoma gene? Knowledge of control of the cell cycle by RB protein does not explain the protein’s tissue speci?city or its importance for retinal development. Following the cloning of RB1, knockout mice were produced, enabling the production and study of homozygotes. The homozygous state is lethal to embryos, with developmental defects in multiple tissues, including the brain. If heterozygous humans did not also develop tumors, we might know RB1 as a recessive, developmental, lethal gene. Can the developmental defects be explained by what is known about control of the cell cycle by RB protein? Apparently not. Now Dyer and colleagues, and other researchers [1] have discovered that RB protein interacts with oth