Tumor suppressor genes (TSGs) are important gatekeepers that protect against somatic evolution of cancer. Losing both alleles of a TSG in a single cell represents a step toward cancer. We study how the kinetics of TSG inactivation depends on the population size of cells and the mutation rates for the first and second hit. We calculate the probability as function of time that at least one cell h...

The transforming growth factor-B (TGF-B) signaling pathway has an important role in regulating normal prostate epithelium, inhibiting proliferation, differentiation, and both androgen deprivation–induced and androgen-independent apoptosis. During prostate cancer formation, most prostate cancer cells become resistant to these homeostatic effects of TGF-B. Although the loss of expression of eithe...

Breast cancer progression is driven by altered gene expression. We show that the RIN1 gene, which encodes a RAS effector regulating epithelial cell properties, is silenced in breast tumor cell lines compared with cultured human mammary epithelial cells. We also report that RIN1 is often reduced in human breast tumor cells compared with morphologically normal breast glandular cells. At least two...

Cancer develops through genetic and epigenetic alterations that allow unrestrained proliferation and increased survival. Using a genetic RNAi screen, we previously identified hundreds of suppressors of tumorigenesis and/or proliferation (STOP) genes that restrain normal cell proliferation. Our STOP gene set was significantly enriched for known and putative tumor suppressor genes. Here, we repor...

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances,...

Endosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gene cluster 3p21.3) drives tumorigenesis in vivo. Indeed, Ptpn23(+/-) loss predi...

Arnold J. Levine, 1. Cathy A. Finlay, 2 and Philip W. Hinds 3 1Institute for Advanced Study Einstein Drive Princeton, New Jersey 08540 and Cancer Institute of New Jersey 195 Little Albany St. New Brunswick, New Jersey 08903 2 Department of High Throughput Biology GlaxoSmithKline 5 Moore Drive Research Triangle Park, North Carolina 27709 3Harvard Medical School Department of Pathology Armenise 4...

The last two decades have led to a greater understanding of the genetic basis of human malignancy. Although numerous genetic alterations have been detected in cancer, activation of oncogenes and inactivation of cell cycle regulators (e.g., tumor suppressor genes) are now known to play a critical role in the progression of the disease. Therapeutic strategies based on specific molecular alteratio...

Tumor suppressor gene p53 and its aggregate have been found to be involved in many angiogenesis-related pathways. We explored the possible aggregation formation mechanisms commonly occur after ischemic stroke, such as hypoxia presence of reactive oxygen species (ROS). The angiogenic pathways involving mainly nucleus or cytoplasm, with one exception that occurs mitochondria. Considering high mit...