The molecular biology of retinoblastoma

Retinoblastoma, a rare pediatric eye tumor, has served as an important mode l for the heritable predisposition to cancer. The retinoblastoma protein, R b, functions as a tumor suppressor by controlling progression through the c ell cycle. Rb function is regulated primarily by its phosphorylation state, which is determined by the complex interaction of multiple kinases and the ir inhibitors that together form the 'Rb pathway'. This pathway has been fo und to be functionally inactivated in almost all types of cancer. Despite r ecent advances in our understanding of Rb function, the precise role of Rb loss in the development of retinoblastoma remains unclear. Recent work in g enetically altered mice has suggested that an additional mutation in anothe r gene is required for retinal tumor formation. An alternative model presen ted here is based on the noncell-autonomous functions of Rb contributing to tumorigenesis.