Searching the Epigenome for Novel Breast Cancer Tumor Suppressors

摘要

Our initial proposal focused on developing technologies to uncover epigenetic changes that contribute to tumor development. Our initial attempts towards developing genome wide approaches to identify new genes silenced by epigenetic mechanisms encountered problems; however, our efforts to exploit epigenetic mechanisms of gene silencing to study tumor suppressor gene function have been very successful (see below). We have built upon these successes both to push the development of broadly useful technologies for the use of RNAi in cell culture, in transgenic animals and in mosaic animals. This has led to insights into the function of tumor suppressor genes and is leading toward the identification of epigenetic regulators that are potentially cancer relevant. Finally, we have found that senescent cells for heterochromatic foci, SAHFs, which may help this innate tumor suppression mechanism to maintain stable growth arrest.