Interestingly, apoptotic cells were markedly increased in VSMC transfected with antisense Rb ODN alone, accompanied by the induction of p53 protein. We finally examined the molecular mechanisms of apoptosis induced by the absence of Rb. Overall, these data first demonstrated that the antioncogenes p53 and Rb negatively regulated the cell cycle in VSMC, suggesting that the modulation of their activity may mediate VSMC growth such as that in restenosis and atherosclerosis. The presence of p53 plays a pivotal role in the regulation of apoptosis in human VSMC growth, probably through the bax pathway. Retinoblastoma, the most common intraocular malignancy ill childhood, has served as a paradigm for the study of genetic mechanisms of oncogenesis.
Human retinoblastoma has essentially no naturally occuring animal counterpart.
The development of transgenic murine models of retinoblastoma have created an experimental tool for manipulation of a tumor gene system in vivo. These models have also enabled studies of new therapeutic modalities. This review outlines the development of the transgenic murine models of retinoblastoma, together with the genetic mechanisms of retinoblastoma origin. Current therapeutic innovations developed by means of the transgenic models are described. Karolinska sjukhuset, Stockholm.